COVID-19

SARS-CoV-2 Update 1/14/23

In 2022, multiple new Omicron variants BA.1, BA.2, BA.4, and BA.5 assaulted the world’s population of humans and other animals. By the time multiple companies made and tested Omicron BA.1 vaccines, BA.1 was no longer the dominant variant; in fact, it was no longer present. On August 31, 2022, the FDA allowed rapid introduction of an Omicron BA.5 bivalent vaccine. However, this has had no effect on new immune evading BQ variants. In December the first highly infectious recombinant variant, XBB, began spreading around the world. An additional variant, XBB.1.5, is now rapidly spreading across the country and the world causing increased numbers of hospitalizations and critically ill patients in the USA. A new variant, CH.1.1 (BA.2.75.3.4.1.1.1.1) caused 5.9% of infections in the world from December 25 to January 14, 2023 and, from December 26 to January 1, 19.5% of infections in the United Kingdom. 

On January 13, the World Health Organization (WHO) updated its recommendations on mask wearing to specify that, given the global spread of COVID-19, masks should be worn “irrespective of the local epidemiological situation,” meaning that masks are now recommended for everyone, not just people in areas with high levels of transmission. Here are our 14-day moving average determinations for SARS-CoV-2 for the United States. We use the WORLDOMETERS aggregators data set to make any projections since it includes data from the Department of Veterans Affairs, the U.S. Military, federal prisons and the Navajo Nation.

XBB.1.5 Variant Continues to Dominate

During the week ending in 1/14/22, the CDC estimates that based on genomic surveillance, XBB.1.5 accounted for 43% of infections, followed by BQ.1.1 at 28.8%, BQ.1 at 15.9%, XBB at 3.9%, BA.5 at 2.6%, BN.1 at 2.1%, BF.7 at 1.4%, and BA.2.75 at 1.3%. The remaining variants made up less than 1% each: BA.5.2.6 (0.5%), BA.2 (0.2%), BF.11 (0.2%), BA.4.6 (0.1%), and BA.2.75.2 (0.1%). We are keeping our eye on BA.2.75, as the CDC is likely lumping in its descendant, CH.1, and its subvariants under this label. 

CDC

BQ.1.1 has five spike mutations that are different from BA.5. Four of these mutations allow escape from immunity from monoclonal antibodies, any prior infection (including Omicron BA.5), or any vaccine to include the bivalent Omicron BA.5 vaccine. Infections are still occurring in our clinic in patients that received the Omicron BA.5 bivalent vaccine. The XBB recombinant isolate XBB.1.5  has rapidly become the dominant infection in the USA. It took 28 days to become the cause of 40% of infections in the USA. As of 1/14/23, XBB.1.5 now causes over 80% of infections in Regions 1 and 2. 

The “Omicron family feud” is a phrase coined by Dr. Raj Rajnarayanan to describe what’s going on between the Omicron BQ variants, BQ.1, BQ,1.1 (and other BQ variants) and XBB.1.5 (and other XBB variants). In the USA in regions 1 and 2, XBB.1.5 has won the feud. A new variant of BA2.75, CH.1.1, is now 4.9% of SARS-CoV-2 isolates in the world. It has the Delta mutation, P681R, which should raise a red flag. According to Saito et al, the P681R mutation, “facilitates cleavage of the spike protein and enhances viral fusogenicity [the ability of the virus to fuse to human cell membranes]….and pathogenicity [lethality].”  

XBB.1.5 Proportion of Sequenced Isolates in the USA

12/3/2212/10/2212/17/2212/24/2212/31/221/7/231/14/23
2.3%4.4%7.4%11.8%20.1%30.4%43.0%

BQ. 1 and BQ.1.1 Totaled Proportion of Sequenced Isolates in the USA

12/3/2212/10/2212/17/2212/24/2212/31/221/7/231/14/23
53.5%57.4%58.6%60.3%59.2%53.2%44.7%

Percent of isolates identified as XBB.1.5 by Region

Region
Week ending in12345678910
12/31/2275.3%72.2%32.7%19.0%6.0%21.5%8.1%2.1%9.2%2.5%
1/14/2381.7%82.7%49.0%31.1%14%24.9%8.8%15%15.8%8.1%
CDC

SARS-CoV-2 infections per day in the United States have increased for the second time in 6 weeks. There is still widespread underreporting by states, a failure to capture all positive home tests, and a decreased PCR screening program in most states. Deaths per day in the United States have increased by 147 deaths per day. Many states are not reporting deaths or infections in a timely manner. The number of infections per day is expected to increase in the next four weeks due to a lack of mask use in schools, businesses, and airports; a failure of adequate building ventilation; lack of social distancing; and low rates of bivalent booster uptake. XBB, an Omicron recombinant variant first identified in India, caused a major outbreak in Singapore. XBB is the first recombinant variant combining spike protein sequences from two other Omicron BA.2 variants, that has spread aggressively around the world. New mutations of XBB, specifically XBB.1.5 are rapidly crowding out other variants in the USA. Current vaccines, monoclonal antibodies and prior infections will not protect you from getting an XBB.1.5 infection. A more detailed description of XBB variant mutations and epidemiology can be found on page 17 of the UK Health Security Agency Technical Briefing from November 25

For a more detailed picture of COVID variant evolution in the United States, we recommend checking out the dashboard put together by Raj Rajnarayanan, Assistant Dean of Research and Associate Professor at NYITCOM at Arkansas State University. 

To understand the true impact of these variants, it’s helpful to examine their evolution. Two virologists collaborated on Twitter to create the figure below, which Professor Johnson titled “Convergent Evolution on Steroids.”  It shows the key mutations present in many of the currently-circulating Omicron subvariants and demonstrates that mutation at site 346 is becoming more and more common. 

From Daniele Focosi, M.D., Ph.D. @dfocosi on Twitter, January 9, 2023

Past infections with a BA.1, BA.2 or BA.5 variants will not prevent infections with any of the newer variants. Monoclonal antibodies are no longer effective against newer BQ variants, XBB variants and other spike protein mutated variants. The last remaining monoclonal antibody, bebtelovimab, was removed from use by the FDA on 12/2/22. Paxlovid was only 89% effective in the original clinical trials against SARS-CoV-2. If resistance develops this winter to oral Paxlovid, we will have more Paxlovid failures and increased hospitalizations and deaths.

A Deeper Dive into U.S. COVID Data

On 1/13/23, the United States had 19,397 documented new infections. There were also 193 deaths. Thirty-seven states did not report their infections, and 37 states didn’t report their deaths. In the United States on 1/13/23 the number of hospitalized patients (44,806)  has increased  (+10.98% compared to the previous 14 days) and was 40,374 on December 30. On 1/13/22 there were 5,449 patients who were seriously or critically ill (a 6.1% increase); that number was 5,135 two weeks ago. The number of critically ill patients has increased by 315 in the last 14 days, while at least 7,064 new deaths occurred. The number of critically ill patients has increased for the 11th time in thirty-five 14-day periods. Patients are still dying each day (average 505/day). 

As of 1/13/23, we have had 1,125,020 deaths and 103,482,187 SARS-CoV-2 infections in the United States. We have had 971,709 new infections in the last 14 days. We are adding an average of 485,855 new infections every seven days. For the pandemic in the United States we are averaging one death for every 91.98 infections or over 10,872 deaths for each one million infections. As of 1/13/22, thirty-nine states have had greater than 500,000 total infections, and 38 states and Puerto Rico have had greater than 5,000 total deaths. Forty-six states have had greater than 2,000 deaths, and 33 states have greater than 3,000 deaths per million population. Nine states have over 4,000 deaths per million population: Mississippi (4,406), Arizona (4,465), Alabama (4,246), West Virginia (4,340), New Mexico (4,240), Tennessee (4,186), Arkansas (4,225), Michigan (4,105) and New Jersey (4,016). Eighteen states (Alabama, Virginia, Missouri, North Carolina, Indiana, Tennessee, Massachusetts, Ohio, Michigan, Georgia, Illinois, New Jersey, Pennsylvania, Florida, Texas, New York, Arizona and California) have had greater than 20,000 deaths. Nine states have had greater than 40,000 deaths: Florida (84,170 deaths), Texas (92,600 deaths), New York (75,909 deaths), Pennsylvania (49,263 deaths), Georgia (41,648 deaths), Ohio (41,001 deaths) , Illinois (40,678 deaths), Michigan (41,001), and  California (98,954 deaths, 20th most deaths in the world). 

On 11/20/20, there were 260,331 (cumulative) deaths in the US from SARS-CoV-2. Since 11/20/20 (26 months), there were 857,919 new deaths from SARS-CoV-2. For twenty-two of those months, vaccines have been available to all adults. During these twenty-two months, 552,821 people have died of SARS-CoV-2 infections. Clearly, a vaccine-only approach is not working anywhere, especially not in the United States. In addition to getting more people vaccinated, most of the hospitalizations and deaths could have been prevented by proper masking (N95 or better), social distancing, and treatment with oral antiviral agents like Paxlovid. We recommend all of these precautions and treatments to every patient in our clinic, and we have only lost one patient to COVID in 2.5 years. 

As of 1/13/23, California was ranked 32nd in the USA in infection percentage at 29.99%. In California, 26.02% of the people were infected in the last 22 months. As of 1/13/23, 31 states have had greater than 30% of their population infected. Fifty states, the District of Columbia and Puerto Rico have greater than 20% of their population infected.                   

FDA-Approved Oral Drug Treatments for SARS-CoV-2

Pfizer has developed PAXLOVID™, an oral reversible inhibitor of C3-like protease of SARS-CoV-2. The drug inhibits this key enzyme that is crucial for virus production. The compound, also called Compound 6 (PF-07321332), is part of the drug combination PAXLOVID™ (PF-07321332; ritonavir), which successfully completed a Phase 2-3 trial in humans in multiple countries. The preliminary results were announced on 11/5/21 by Pfizer. The results showed that 89% of the hospitalizations and deaths were prevented in the drug treatment arm. The drug was administered twice a day for five days. No deaths occurred in the treatment group, and ten deaths occurred in the placebo group. The study was stopped by an independent data safety monitoring board, and the FDA concurred with this decision. Pfizer applied for an Emergency Use Authorization for this drug on 11/15/21. This drug was approved on 12/23/21. PAXLOVID™ one year later is widely available at major pharmaceutical chains and smaller independent drug stores throughout the USA. We have  been able to obtain PAXLOVID™ for any patient desiring treatment. We have only had one  drug failure and death from SARS-CoV-2 during 2022. That death occurred in an octogenarian male in the fourth quarter of 2022.

Watching World Data

Over the next few months, we’ll be paying close attention to correlations between the SARS-CoV-2 data, the number of isolates identified in various countries and states, and the non-pharmaceutical interventions (like mask mandates and lockdowns) put in place by state and national governments. Data on infections, deaths, and percent of population infected was compiled from Worldometers. Data for this table for SARS-CoV-2 Isolates Currently Known in Location was compiled from GISAID and the CDC. It’s worth noting that GISAID provided more data than the CDC.

LocationTotal Infections as of 1/13/23New Infections on 1/13/23Total DeathsNew Deaths on 1/13/23% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World670,816,950319,9876,728,2701,6078.60%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617.2 (India)BV-1 (Texas, USA)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Theta/P.3 (Philippines) Mu/B.1.621 (Colombia)C.1.2 (South Africa 2% of isolates in July 2021)R1 (Japan)Omicron/B.1.1.529 + BA.1 + BA.2 + BA.3 (South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)Four new recombinants 12/31 to 3/22)BA.2.12.1 (USA)BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)BF.7BJ.1XBBBQ.1BQ.1.1BS.1BN.1  NoNo
USA103,482,187 (ranked #1)
19,397 (ranked #5)
37 states and D,C. failed to report infections on 12/2/22.
1,125,020 (ranked #1) 193
37 states  and D.C. failed to report deaths on 1/13/23.
30.90%
B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan)         Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)Recombinant Delta AY.119.2- Omicron BA.1.1 (Tennessee, USA 12/31/21)\BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)BQ.1BQ.1.1BN.1NoNo
Brazil36,623,217(ranked #5) 20,548 (ranked#4)695,334 (ranked #2)7917.00%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)NoNo
India 44,681,884 (ranked #2)
530,726(ranked #3) 3.17%
Unchanged in 4 weeks
B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)APTK India VOI 32421Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Iota/B.1.526 (USA-NYC) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India)NoNo
United Kingdom
24,243,576 (ranked #9)202,157 (ranked #7) 470 new deaths in 2 weeks35.39%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)C.1.2 (South Africa)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)XD (AY.4/BA.1) recombinantXF (Delta/BA.1) recombinantXE (BA.1/BA.2) recombinantBA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)NoNo
California, USA11,852,546 (ranked #13 in the world)1,51698,954 (ranked #20 in world)
2529.99%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)BQ.1BQ.1.1BN.1NoNo
Mexico7,303,600 (ranked #19) 5,686 (ranked #11)331,452(ranked #5)455.55%NoNo
South Africa4,051,243 (ranked #37; 4,347 new infections in 14 days).183102,568 (ranked #18) 0 new deaths in 14 days)
Unchanged in 4 weeks
6.66%


Unchanged in 4 weeks
B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)       C.1.2 (South Africa, July 2021)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)NoNo
Canada4,508275 (ranked #34)49,566 (ranked #24 ) 11.74% NoNo
Poland6,732,901 (ranked #21)324118,640 (ranked #15) 87 new deaths in the last 14 days716.88%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3 NoNo
Russia21,846,722 (ranked #10)5,978 (ranked #12)394,209(ranked #4)4714.98%NoNo
Peru4,473,821(ranked #35)627 218,490(ranked #6) 1313.28%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Iran7,562,446 (ranked #18)75144,723 (ranked #12) 18.78%
Unchanged in 4 weeks
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Spain13,711,251 (ranked #12)9,871 (ranked #7)117,759 (ranked #16) new deaths in 14 days7629.34%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
France39,442,176 (ranked #3)6,238 (ranked #9)163,347 (ranked #10)10160.13% B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinantBQ.1.1NoNo
Germany37,605,135 (ranked #4)10,609 (ranked #6)163,775 (ranked #9)15044.83%
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantBQ.1.1NoNo
South Korea29,737,769 (ranked #7)39,726 (ranked #2)32,867 (ranked #34) 6657.93%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Vietnam11,526,089 (ranked #13)5543,186(ranked #26)11.64%
Unchanged in 4 weeks
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021),No
Netherlands8,576,523 (ranked #17)22,989 (ranked #41)49.83%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
Denmark3,171,515 (ranked #40)  1907,982 (ranked #76)1154.35%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo




Taiwan9,167,795 (ranked #16)21,721 (ranked #3)15,755 (ranked #56)
5338.37%
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Japan31,176,281(ranked #6)144,077 (ranked #1)61,761(ranked #23)
48024.82%
14 days.
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)BA.2*BA.5*NoNo
Argentina10,004,679 (ranked #15)130,249(ranked #14)21.74%NoNo
Italy25,363,742 (ranked #8) 185,993(ranked #8) 42.08%
NoNo
Chile5,081,862 (ranked #27)3,289 (ranked#14)63,466(ranked #22) 
2926.39%
NoNo
Colombia6,349,971 (ranked #22) 142,259(ranked #13)12.32%
NoNo
Australia11,247,412 (ranked #14) 5,985 (ranked #10)17,712(ranked #50) 5943.14% 
NoNo
Turkey17,042,722 (ranked #11)101,492 (ranked #19)   19.91%
Unchanged in 4 weeks
NoNo


Indonesia6,725,458 (ranked #20)363160,719 (ranked #11)   478 new deaths in the last 14 days.824.09%NoNo
Malaysia5,032,146 (ranked #28) 32036,908 (ranked #29) 315.16%NoNo


Hong Kong2,817,707(ranked#41) 8,260 (ranked #8)12,693 (ranked#60) 345 new deaths in the last 14 days.7137.05%
NoNo
China503,302 (ranked #91)

What Our Team Is Reading This Week

COVID-19

Pandemic Year 3 in Review

When my daughter, Emily, and I started writing this blog in the spring of 2020, we did not anticipate that almost three years later, there would still be no end in sight for this pandemic. As we begin a new year, we wish we had better news, but the data continues to tell a grim story, and, as our long-time readers know, we always ground our outlook in the numbers. 

In the United States, from March 2020 to December 31, 2021, we had 55,696,500 SARS CoV-2 infections and 846,905 deaths (66 infections per death). In the last 12 months we have had an additional 46,813,072 new infections and an additional 271,051 deaths (173 infections per death). That’s an average of 742 deaths per day. The majority of these deaths were in people over the age of 65, and all of them were preventable. In November 2022, KFF reported that COVID-19 was still the number 3 cause of death in the United States. It’s also worth noting that the number one cause of death, cardiovascular disease, is a known complication of COVID

In late December 2021 the FDA approved both oral Paxlovid and oral Molnupiravir for outpatient treatment of SARS-CoV-2 with distribution beginning in January 2022. Unfortunately, all of the mask mandates were removed by individual states in 2022, and despite President Biden’s vow to institute a federal mask mandate during his 2020 campaign, the President and his administration adopted a decidedly anti-mask policy this year. CDC Director Rochelle Walensky even went so far as to describe masks as “the scarlet letter of this pandemic.” This irresponsible public health messaging has led to thousands of infections and deaths that could have been otherwise prevented by responsible mask wearing. We continue to urge our patients to protect themselves and others by wearing an N95 (or better) mask in public.

This year, multiple new Omicron variants BA.1, BA.2, BA.4, and BA.5 assaulted the world’s population of humans and other animals. By the time multiple companies made and tested Omicron BA.1 vaccines, BA.1 was no longer the dominant variant; in fact, it was no longer present. On August 31, 2022, the FDA allowed rapid introduction of an Omicron BA.5 bivalent vaccine. However, this has had no effect on new immune evading BQ variants. In December the first highly infectious recombinant variant, XBB, began spreading around the world. An additional variant, XBB.1.5, is now rapidly spreading across the country and the world causing increased numbers of hospitalizations and critically ill patients in the USA. 

At the same time, we have had outbreaks and deaths from Influenza A H3N2 and RSV. Travel and lack of masking and social distancing have exacerbated the spread of these viruses. In addition, Mpox virus outbreaks occurred nationwide, a measles outbreak began in Ohio in unvaccinated children, and several cases of polio in New York were reported. 

Part of why the United States’ vaccine-only approach to COVID-19 is so dangerous is that SARS-CoV-2 mutates, evading immune protection, and spreads more quickly than anyone can make, get approved, and distribute new vaccines. The Omicron BQ.1.1 variant is now being rapidly replaced by XBB.1.5.  As an example, at D4 Labs, we designed, manufactured and packaged a new vaccine for Omicron BQ.1.1 in 6 weeks. Minimal animal testing, IRB approval, human testing, and expedited FDA approval under an EUA would probably require at least another 6 months. Even if we skipped or delayed animal testing, obtained IRB approval, and internally did a standard two-dose immunogenicity study in 20 humans using IgG antibody to the RBD of SARS-CoV-2 as the surrogate marker for protection, it would still take three months in our in-house human testing and assay facility to complete the study. This approach would probably not be acceptable to the FDA for even EUA approval but might be attempted in individual states. The timely production and distribution of any new vaccine against any new SARS-CoV-2 mutant will be difficult to accomplish by any company using the current regulatory framework for approval of vaccines in the United States. Using XBB.1.5 as an example, it is responsible for over 40% of the infections in the United States in the last 28 days. Vaccines would have to be designed, manufactured, and distributed in less than four weeks to stop an outbreak of a virulent, highly-infectious respiratory pathogen. Considerable thought needs to be entertained on how to accomplish this task rapidly. 

Sadly, we do not see things improving in 2023 for respiratory virus control in the United States unless people wear high quality masks (N95 or better) and practice social distancing again. Continued infection and death increases are expected in the next eight weeks with 113 million people expected to travel during the holiday season, schools reopening on January 2, and people returning to work in poorly ventilated spaces. 

Here are our 14-day moving average determinations for SARS-CoV-2 for the United States. We use the WORLDOMETERS aggregators data set to make any projections since it includes data from the Department of Veterans Affairs, the U.S. Military, federal prisons and the Navajo Nation.

After Delays, CDC Discloses XBB.1.5 Variant Data

On 12/31/22 the CDC estimates that BA.5 accounted for 3.7% of infections (a 49.6% point drop from its peak), BQ.1 accounted for 18.3% (a 12.4% point drop decrease from its peak on 12/17/22), BQ.1.1 accounted for 26.9% (a 11.5% point drop from its peak on 12/17/22), BA.4.6 accounted for 0.3%, BF.7 accounted for 2.1% of infections, BN.1 accounted for 2.4% of isolates, and BA.2.75.2 accounted for 0.1%. XBB is 3.6% of isolates, XBB.1.5 is 40.5% of isolates, BA.5.2.6 is 0.6% of isolates, and BF.11 0.3% of isolates. In the week ending December 31, 2022, BQ isolates accounted for 45.2% of isolates (a 23.9% point decrease in infections caused by these BQ variants since 12/17/22). 

CDC

BQ.1.1 has five spike mutations that are different from BA.5. Four of these mutations allow escape from immunity from monoclonal antibodies, any prior infection (including Omicron BA.5), or any vaccine to include the bivalent Omicron BA.5 vaccine. Infections are still occurring in our clinic in patients that received the Omicron BA.5 bivalent vaccine. The XBB recombinant isolate XBB.1.5  has rapidly become the dominant infection in the USA. It took 28 days to become the cause of 40% of infections in the USA and it now causes over 70% of infections in Regions 1 and 2.

XBB.1.5 Proportion of Sequenced Isolates in the USA

12/03/2212/10/2212/17/2212/24/2212/31/22
1.3%3.7%9.9%21.7%40.5%

XBB.1.5 by Region on 12/31/22

Region12345678910
Percent of isolates identified as XBB.1.575.3%72.2%32.7%19.0%6.0%21.5%8.1%2.1%9.2%18.2%
CDC

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COVID-19

SARS-CoV-2 Update

It’s time for our next 14-day moving average determinations for SARS-CoV-2 for the United States and my thoughts on vaccines, SARS-CoV-2 therapeutic agents and mutant viruses. We use the WORLDOMETERS aggregators data set to make any projections since it includes data from the Department of Veterans Affairs, the U.S. Military, federal prisons and the Navajo Nation.

SARS-CoV-2 infections per day in the United States have increased for the first time in 14 weeks. There is still widespread underreporting by states, a failure to capture positive home tests, and a decreased PCR screening program in most states. Deaths per day in the United States have increased by 34 deaths per day. Many states are not reporting deaths or infections in a timely manner. The number of infections per day has increased by 1,683.  The CDC estimates that BA.5 accounted for 39.2% (a 23% drop from 10/21/22), BQ.1 accounted for 16.5% (a 7.1% increase since 10/21/22), BQ.1.1 accounted for 18.8% (a 11.6% increase since 10/21/22), BA.4.6 accounted for 9.5%, BF.7 accounted for 9%,  BA.2.75.2 accounted for 1.3%, and BA.4 accounted for 0.2%. In the week ending November 5, 2022 BQ isolates accounted for 35.3% of infections. BQ.1.1 has five spike mutations that are different from BA.5. Four of these mutations allow escape from immunity from monoclonal antibodies, any prior infection (including BA.5), or any vaccine to include a BA.5 vaccine. 

CDC
CDC

The total percentage of BQ variant infections in the region that includes New York and New Jersey was 28.4% two weeks ago and is now 52.3%. BA.5.2.6 isolates now account for 3.1% of cases. The BA.2.75 lineages account for 4.2%. 

CDC

The total percentage of BQ variant infections in the region that includes Pennsylvania, Delaware, Maryland, West Virginia, and Virginia was 17.8% two weeks ago and is now 36.6%. BA.5.2.6 isolates now account for 3.4% of cases. The BA.2.75 lineages account for 3% of cases. 

CDC

The total percentage of BQ variant infections in the region that includes California, Nevada, Arizona, and Hawaii was 13.6% two weeks ago and is now 36.9%. BA.5.2.6 isolates now account for 2.4% of cases. The BA.2.75 lineages account for 4.2%. 

Data on the rapid spread of a dangerous variant category, the BQ variants, was withheld by the CDC in their weekly reports until three weeks ago. The data on BQ.1 and BQ.1.1, the last being a variant with five significant spike protein mutations leading to escape from immunity from prior infections or vaccination. In addition, our monoclonal antibody therapies do not work for these isolates. Infections and hospitalizations in New York are rapidly increasing, secondary to BQ variants. BQ variants have been found in all 10 regions in the United States. Since New York has been a harbinger of things to come throughout the pandemic, we expect the pattern of increased infections, hospitalizations and deaths to continue in many states. These emerging BQ variants are descendants of BA.5. It’s troubling that, despite the availability of a BA.5 bivalent SARS-CoV-2 vaccine, few people are getting vaccinated. As of November 2, 2022, the CDC reports that only 26,378,963 people have received the bivalent vaccine. The Pfizer Omicron BA.5 mRNA booster was administered to 16,748,737 people and the Moderna Omicron BA.5 mRNA booster was administered to 9,630,226 people. In total, 26.3 million people (5 years and up) have received the bivalent vaccine. That’s only 11.6% of people who received the primary series and 7.9% of the overall population.  

Children under the age of 5 have not been approved to receive either Omicron BA.5 mRNA boosters. Sadly, in children between 0 and 5 years of age only 1.47 million have received at least one dose of any SARS-CoV-2 mRNA vaccine. In the United States, at least 1,332 children have died of COVID-19, and another 74 have died of multisystem inflammatory syndrome (MIS-C). Worldwide, according to UNICEF, over 16,100 children and young adults aged 0-20 have died of COVID-19. 

The October 28 UK Health Security Agency Technical Briefing identifies lineages BQ.1, BQ.1.1, XBB, and BF.7 as isolates of concern. Although BA.5 remains the dominant lineage in the UK, the authors explain, “In the most recent week, logistic growth of variants with 1, 2 or 3 convergent and antigenically significant RBD mutations was respectively 23%, 47%, and 66% per week. The category with 3 RBD mutations consisted largely of BQ.1.1 (59%) with the remainder consisting primarily of a mixture of BA.2.75 sub-lineages (29%).” 

VariantSublineage ofSpike MutationsGlobal SequencesUK Sequences
BF.7BA.5.2.1R346T11,9222,644
BQ.1BA.5L452RN460KK444T2,4903,207
BQ.1.1BA.5N460KK444TR346T2,304(35 countries)1,272
BS.1BA.2.3.2R346TL452RN460KG476S79 2
Data from UK Health Security Agency

In Monterey County, as of 11/5/22, 2.6% of 0-4 year-olds and 40.1% of 5-11 year-olds have received the first two doses of vaccine, while 73.4% of 12-17 year-olds have received two doses. Only 54.5% of Monterey County residents have received a third dose of the vaccine. The Monterey County Health Department does not publish data on how many residents have received the new BA.5 bivalent booster vaccine. On June 17, The FDA authorized both the Pfizer and Moderna vaccines for use in children ages 6 months to four years. We believe children under 5 should be vaccinated as soon as possible. All Monterey County residents should get up to date on COVID-19 vaccinations, including the bivalent BA.5 booster, as soon as possible. 

Monterey County Health Department

On 11/04/22, the United States had 21,312 documented new infections. There were also 148 deaths. Thirty-five states did not report their infections, and 37 states didn’t report their deaths. In the United States the number of hospitalized patients has increased slightly (+2% compared to the previous 14 days) in many areas and was 27,395 on November 5. On 11/05/22 there were 3,146 patients who were seriously or critically ill; that number was 2,707 two weeks ago. The number of critically ill patients has increased by 439 in the last 14 days, while at least 5,432 new deaths occurred. The number of critically ill patients has decreased for the sixth time in thirty 14-day periods. Patients are still dying each day (average 388/day). Two new Omicron variants BQ.1 and BQ.1.1 are causing increased numbers of infections and hospitalizations in New York. BA.4, BA.4.6, BA.5, and BF.7 variants are still causing infections. In Singapore a different Omicron BA.2 variant, XBB, has caused rapidly increasing infections and now has been named a designated variant along with BQ.1 in the October 28 UK Health Security Agency Technical Briefing. Past infections with a BA.1, BA.2 or BA.5 variants will not prevent infections with any of the newer variants. 

As of 11/04/22, we have had 1,098,038 deaths and 99,602,478 SARS-CoV-2 infections in the United States. We have had 546,941 new infections in the last 14 days. We are adding an average of 273,348 new infections every seven days. For the pandemic in the United States we are averaging one death for every 90.71 infections or over 11,024 deaths for each one million infections. As of 11/04/22, thirty-eight states have had greater than 500,000 total infections, and 38 states have had greater than 5,000 total deaths. Forty-six states have had greater than 2,000 deaths, and 43 states have greater than 2,000 deaths per million population. Seven states have over 4,000 deaths per million population: Mississippi (4,365), Arizona (4,338), Alabama (4,193), West Virginia (4,202), New Mexico (4,132), Tennessee (4,118), and Arkansas (4,148). . Eighteen states (Alabama, Virginia, Missouri, North Carolina, Indiana, Tennessee, Massachusetts, Ohio, Michigan, Georgia, Illinois, New Jersey, Pennsylvania, Florida, Texas, New York, Arizona and California) have had greater than 20,000 deaths. Eight states have had greater than 40,000 deaths: Florida (82,357 deaths), Texas (91,737 deaths), New York (73,549 deaths), Pennsylvania (47,840 deaths), Georgia (40,696 deaths), Ohio (40,249 deaths) , Illinois (40,058 deaths), and  California (96,984 deaths, 20th most deaths in the world). 

On 11/20/20, there were 260,331 (cumulative) deaths in the US from SARS-CoV-2. Since 11/20/20 (23 months), there were 830,937 new deaths from SARS-CoV-2. For nineteen of those months, vaccines have been available to all adults. During these nineteen months, 525,939 people have died of SARS-CoV-2 infections. Clearly, a vaccine-only approach is not working anywhere, especially not in the United States. In addition to getting more people vaccinated, most of the hospitalizations and deaths could have been prevented by proper masking (N95 or better), social distancing, and treatment with oral antiviral agents like Paxlovid. We recommend all of these precautions and treatments to every patient in our clinic, and we have only lost one patient to COVID in 2.5 years. 

As of 11/04/22, California was ranked 33rd in the USA in infection percentage at 28.73%. In California, 24.76% of the people were infected in the last 20 months. As of 11/06/22, 24 states have had greater than 30% of their population infected. Fifty states have greater than 20% of their population infected.                            

Worldwide, average deaths per day are 1,637 for the last 14 days, which is a 68 deaths-per-day increase over the previous 14 days. The United States accounts for 23.70% (388 per day) of all deaths per day in the world over the last two weeks. Worldwide infections per day were 346,369. The United States accounts for 11.28% of those infections (or 39,067 infections per day). 

FDA-Approved Oral Drug Treatments for SARS-CoV-2

Pfizer has developed PAXLOVID™, an oral reversible inhibitor of C3-like protease of SARS-CoV-2. The drug inhibits this key enzyme that is crucial for virus production. The compound, also called Compound 6 (PF-07321332), is part of the drug combination PAXLOVID™ (PF-07321332; ritonavir), which just successfully completed a Phase 2-3 trial in humans in multiple countries. The preliminary results were announced on 11/5/21 by Pfizer. The results show that 89% of the hospitalizations and deaths were prevented in the drug treatment arm. The drug was administered twice a day for five days. No deaths occurred in the treatment group, and ten deaths occurred in the placebo group. The study was stopped by an independent data safety monitoring board, and the FDA concurred with this decision. Pfizer applied for an Emergency Use Authorization for this drug on 11/15/21. This drug was approved on 12/23/21. We have only been able to obtain PAXLOVID™ for two patients who we successfully treated with this drug obtained from CVS in Salinas (East Alisal Street; phone number 831-424-0026). They were expecting another shipment on 1/28/22. In my opinion, this agent, if more widely available, could markedly alter the course of every coronavirus infection throughout the world. 

Merck has developed the oral drug Molnupiravir, which induces RNA mutagenesis by viral RNA-dependent RNA polymerase of SARS-CoV-2 and other viruses. According to Kabinger et al, “Viral RNA-dependent RNA polymerase uses the active form of Molnupiravir, β-D-N4-hydroxycytidine triphosphate, as a substrate instead of cytidine triphosphate or uridine triphosphate. When the RNA-dependent RNA polymerase uses the resulting RNA as a template, β-D-N4-hydroxycytidine triphosphate directs incorporation of either guanine or adenine, leading to mutated (viral) RNA products. Analysis of RNA-dependent RNA polymerase–RNA complexes that contain mutagenesis products has demonstrated that β-D-N4-hydroxycytidine (the active form of Molnupiravir) can form stable base pairs with either guanine or adenine in RNA-dependent RNA polymerase explaining how the polymerase escapes proofreading and synthesizes mutated RNA” (quotation modified for clarity). The results of the phase 3 trial of Molnupiravir were published in the NEJM article “Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients” by Angélica Jayk Bernal, M.D. et al. (December 16, 2021 DOI: 10.1056/NEJMoa2116044). In this phase 3 study in the Molnupiravir group, 28 patients were hospitalized and one death occurred. In the placebo group, 53 patients were hospitalized and 9 died. Overall, 47% of hospitalizations and deaths were prevented by Molnupiravir. If you do a post hoc analysis and just look at deaths, Molnupiravir would prevent 89% of deaths. An Emergency Use Authorization by the FDA for Molnupiravir was approved on 12/24/21.The dose of Molnupiravir approved is four 200 mg capsules orally twice a day for five days. Diarrhea is reportedly a side effect in two percent of patients. I treated my first patient with Molnupiravir on 1/28/22. Currently more Molnupiravir is available weekly in the United States than PAXLOVID™ (see chart below; data from PHE.gov). Locally Molnupiravir is still available at CVS in Monterey (Fremont Blvd.; phone number: 831-375-5135) and CVS in Salinas (East Alisal Street; phone number 831-424-0026). 

 28, p740–746 (2021)with four 200 mg capsules orally twice a day for five dayfour 200 mg capsules orally twice a day for five daysIntravenous Drug Treatment for non-hospitalized SARS-CoV-2 Infected Patient

FDA-Approved Intravenous Monoclonal Antibody Treatment for Non-Hospitalized SARS-CoV-2 Patients 

Bebtelovimab is a monoclonal antibody treatment for mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options approved or authorized by FDA are not accessible or clinically appropriate. The authorized dose of bebtelovimab is 175 mg, given as an intravenous injection over at least 30 seconds. The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for this drug on 2/11/22. Bebtelovimab is a human antibody that demonstrates neutralization against the Omicron variants and is available in every state and many hospitals and some clinics. If you are planning on using a monoclonal antibody to treat a SARS-CoV-2 infection, currently only bebtelovimab has activity against all Omicron variants, including BA.4.6. Researchers at Columbia University recently reported that “The loss of activity of tixagevimab and cilgavimab [components of Evusheld] against BA.4.6 leaves us with bebtelovimab as the only therapeutic mAb that has retained potent activity against all circulating forms of SARS-CoV-2.” For this reason, we no longer recommend Evusheld for immunocompromised patients with Omicron infections. 

An examination of the three variants that Wang et al identified as capable of immune escape in patients who receive the two monoclonal antibodies that are contained in Evusheld reveals that all three variants have a mutation in the spike protein at position 346. The changes substitute an uncharged amino acid— threonine (T), serine (S), or isoleucine (I)—for a positively-charged amino acid, arginine. This just goes to show that a single point mutation in the spike protein can render a monoclonal antibody treatment ineffective. Policy makers should keep in mind that the only way to prevent new drug-resistant variants like BA.4.6 from emerging is to prevent transmission of SARS-CoV-2 in the first place, using non-pharmaceutical interventions. The lack of use of N95 masks, with impending winter and influenza outbreaks, on top of COVID-19, is not wise public health and infectious disease policy. If we don’t make effective use of the non-pharmaceutical interventions available to us (masks, ventilation, social distancing), then the pharmaceutical interventions we have will all eventually be useless. 

Two virologists collaborated on Twitter to create the figure below, which Professor Johnson titled “Convergent Evolution on Steroids.”  It shows the key mutations present in many of the currently-circulating Omicron subvariants and demonstrates that mutation at site 346 is becoming more and more common. This means that even if prevalence of BA.4.6 wanes, we are still likely to have drug resistance issues with other newer variants. 

From Daniele Focosi, M.D., Ph.D. @dfocosi on Twitter 

Watching World Data

Over the next few months, we’ll be paying close attention to correlations between the SARS-CoV-2 data, the number of isolates identified in various countries and states, and the non-pharmaceutical interventions (like mask mandates and lockdowns) put in place by state and national governments. Data on infections, deaths, and percent of population infected was compiled from Worldometers. Data for this table for SARS-CoV-2 Isolates Currently Known in Location was compiled from GISAID and the CDC. It’s worth noting that GISAID provided more data than the CDC.

LocationTotal Infections as of 11/04/22New Infections on 11/04/22Total DeathsNew Deaths on 11/04/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World637,281,842(4,849,164 new infections in 14 days).273,3336,604,448(22,918 new deaths in last 14 days)1,0918.17%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617.2 (India)BV-1 (Texas, USA)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Theta/P.3 (Philippines) Mu/B.1.621 (Colombia)C.1.2 (South Africa 2% of isolates in July 2021)R1 (Japan)Omicron/B.1.1.529 + BA.1 + BA.2 + BA.3 (South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)Four new recombinants 12/31 to 3/22)BA.2.12.1 (USA)BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)BF.7BJ.1XBBBQ.1BQ.1.1BS.1  NoNo
USA99,602,478(ranked #1) 546,941 new infections in the last 14 days or 39,067/day.
19,652(ranked #6)
35 states and D,C. failed to report infections on 11/04/22.
1,098,038(ranked #1) 5,432 new deaths reported in the last 14 days or 388/day. 148
37 states  and D.C. failed to report deaths on 11/04/22.
29.74%
B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan)         Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)Recombinant Delta AY.119.2- Omicron BA.1.1 (Tennessee, USA 12/31/21)\BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)NoNo
Brazil34,890,243(ranked #5) 62,069 new infections in the last 14 days. 2,738688,384(ranked #2; 803 new deaths in 14 days)6816.20%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)NoNo
India 44,659,447(ranked #2); 18,699  new infections in 2 weeks.1,082
530,486(ranked #3) 1,529 new deaths in 2 weeks.73.17%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)APTK India VOI 32421Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Iota/B.1.526 (USA-NYC) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India)NoNo
United Kingdom
23,930,041(ranked #7) 74,519 new infections in 2 weeks.194,704 (ranked #7) 2,022  new deaths in 2 weeks34.93%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)C.1.2 (South Africa)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)XD (AY.4/BA.1) recombinantXF (Delta/BA.1) recombinantXE (BA.1/BA.2) recombinantBA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)NoNo
California, USA11,353,896(ranked #13 in the world; 21,351 new infections in the last 14 days).1,43496,984 (ranked #20 in world)
303 new deaths in the last 14 days
728.73%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)NoNo
Mexico7,113,132(ranked #19) 7,114 new infections in 14 days).628330,415(ranked #5)94 new deaths in 14 days)55.40%NoNo
South Africa4,029,737(ranked #37; 4,362 new infections in 14 days).241102,363 (ranked #18) 106 new deaths in 14 days)526.63%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)       C.1.2 (South Africa, July 2021)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)NoNo
Canada4,336,860(ranked #33) 22,142 new infections in 14 days).46,389(ranked #25 ) 364  new deaths in the last 14 days11.29% NoNo
Poland6,333,591 (ranked #21; 9,506  new infections in 14 days). 693118,157 (ranked #15)142 new deaths in the last 14 days1416.80%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3 NoNo
Russia21,453667(ranked #10), 98,753 new infections in 14 days).6,149 (ranked #9)390,459(ranked #4)1,100 new deaths in 14 days7114.71%NoNo
Peru4,159,132(ranked #36, 7,113new infections in 14 days). 598216,972(ranked #6) 95 new deaths in the last 14 days512.34%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Iran7,558,002(ranked #17; 2,308 new infections in last 14 days)40144,587(ranked #12) 47 new deaths in the last 14 days48.78%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Spain13,529,643(ranked #12;   41,628 new infections in 14 days).2,551115,239 (ranked #16)381 new deaths in 14 days2328.95%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
France36,920,064 (ranked #3; 395,459 new infections in the last 14 days).29,438 (ranked #4)157,277 (ranked #10)940 new deaths in 14 days.7856.29%  a 0.60% increase in 14 days.B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinantNoNo
Germany35,823,771(ranked #4; 651,078 new infections in 14 days.)38,859 (ranked #2)154,535 (ranked #11)2,053 new deaths in 14 days 20742.70%
0.77% increase in 14 days
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
South Korea25,760,701 (ranked #6 516,446 new infections in 14 days).43,424(ranked #1)29,315 (ranked #36) 363 new deaths in 14 days3549.18%1.00% increase in 14 daysB2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Vietnam11,505,249 (ranked #13; 8,895 new infections in 14 days).33943,165(ranked #26)11.62%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Netherlands8,521,729 (ranked #16; 27,024 new infections in 14 days).1,22522,845 (ranked #41)349.51%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
Denmark3,138,750 (ranked #40) 7,601 new infections in 14 days. 3557,387 (ranked #78 139 new deaths in the last 14 days)1253.79%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo




Taiwan7,837,658(ranked #17)458,453 new infections in 14 days27,594 (ranked #5)13,084 (ranked #59 878 new deaths in the last 14 days)
7432.80%
1.91% of population has been infected in the last 14 days
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Japan22,534,377(ranked #9)608,146 new infections in the last 14 days34,064(ranked #5)46,898(ranked #24)
757 new deaths in the last 14 days
5917.94%
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)BA.2*BA.5*NoNo
Argentina9,718,875 (ranked #15)129,991(ranked #14)21.12%NoNo
Italy23,642,011 (ranked #8)     179,436(ranked #8)39,23%NoNo
Chile4,777,208(ranked #28)7,57061,737(ranked #22)1224.81%NoNo
Colombia6,310,332(ranked #14)141,850(ranked #13)12.25%NoNo
Australia9,718,875(ranked #14)15,618 (ranked #7)15,776(ranked #55)5939.95%NoNo
Turkey16,919,638(ranked #11)101,203(ranked #19)19.77%NoNo
Indonesia6,512,913 (ranked #20)5,303 (ranked #11)158,768 (ranked #9)3123,23%NoNo
Malaysia4,918,917 (ranked #29)4,360 (ranked #13)36,481 (ranked #29)114.75%NoNo

What Our Team Is Reading This Week

COVID-19

SARS-CoV-2 Update

It’s time for our next 14-day moving average determinations for SARS-CoV-2 for the United States and my thoughts on vaccines, SARS-CoV-2 therapeutic agents and mutant viruses. We use the WORLDOMETERS aggregators data set to make any projections since it includes data from the Department of Veterans Affairs, the U.S. Military, federal prisons and the Navajo Nation.

SARS-CoV-2 infections per day in the United States have decreased for the second time in four weeks; however, there is still widespread underreporting by states, a failure to capture positive home tests, and a decreased PCR screening program in most states. Deaths per day in the United States have decreased by 14 deaths per day. The number of infections per day has decreased by 19,313.  The CDC estimates that BA.5 accounted for 83.1%, BA.4.6 accounted for 11.9%, BF.7 accounted for 2.3%, BA.4 accounted for 1.4%, BA.2.12.1 accounted for 0.0% of isolates, BA.2 accounted for 0.0%, BA.1.1 accounted for 0.0%, and B.1.1.529 accounted for 0% in the week ending September 10. The rise in BA.4.6 cases is especially concerning because the September 9 UK Security Agency Technical Briefing says that, “Pseudoviral neutralisation assays performed on BA.4.6 show that titres are reduced 2-fold, compared to neutralisation of BA.4 or BA.5 using sera from triple dosed recipients of the Pfizer BNT162b2 vaccine.” The same briefing also states that BA.4.6 has a growth advantage relative to BA.5. 

CDC

We frequently hear messaging from health officials and politicians that Omicron is “mild,” especially compared to the Delta variant, and as a result, many of our patients believe that they no longer need to wear their masks. This is a dangerous misconception. SARS-CoV-2 still remains a highly transmissible, airborne virus. The following graph, based on CDC data from April 2, 2022, shows that Omicron deaths in people over 65 are much higher than Delta deaths in the same age group. In fact, the peak of Omicron deaths in people over 65 years of age is 163% higher than the Delta peak. The death rate from Omicron is only lower than Delta in the populations between 12 and 64 years of age. Until we have more data on these newer mutants of SARS-CoV-2, we will not know the lethality of each variant. It may take months to measure objective differences in the death rates of new circulating variants. We recommend that all of our patients and family members continue to wear N95 masks in all enclosed spaces.

In patients treated with Paxlovid for five days who have persistent symptoms and continued positivity, we feel that clinicians should consider giving a second course of Paxlovid for five days. Boucau et al have demonstrated that in a study of seven patients with recurrent symptoms, “High viral loads (median 6.1 log10 copies/mL) were detected after rebound for a median of 17 days after initial diagnosis. Three had culturable virus for up to 16 days after initial diagnosis.” This was not due to resistance-associated mutations of the virus, suggesting that the course of therapy may be inadequate in this group of persistently infected patients. 

NY Times

The Omicron variant has continued to mutate just like Delta. The list of variants was not updated in the last four weeks, but as of six weeks ago, there are now 276 Omicron sub-variants that have been assigned Pango lineages, including 123 sub-lineages of BA.2, one sub-lineage of BA.3, 15 sub-lineages of BA.4, and 45 sub-lineages of BA.5. The BF lineage (new fourteen weeks ago) now has 21 sublineages.. The BE lineage (also new fourteen weeks ago), with BE.1 first detected in South Africa, Austria and England, now has 7 sublineages. There are also new lineages from fourteen weeks ago: BC.1 (Japan), BC.2 (Peru), BD.1 (UK), BG.1 (Peru), BG.2 (US, Denmark, Canada), BG.3 (Peru), BG.4 (Israel). In the last six weeks, the BG lineage has expanded to include BG.5 (USA) and BG.6 (Peru). Lastly, two new sublineages were added in the past six weeks: BH.1 (India) and BK.1 (USA and Canada). 

In Monterey County, as of 9/24/22, 1.1% of 0-4 year-olds and 39.9% of 5-11 year-olds have received the first two doses of vaccine, while 73.1% of 12-17 year-olds have received two doses. Only 53.6% of Monterey County residents have received a third dose of the vaccine. On June 17, The FDA authorized both the Pfizer and Moderna vaccines for use in children ages 6 months to four years. We believe children under 5 should be vaccinated as soon as possible. All Monterey County residents should get up to date on COVID-19 vaccinations as soon as possible. 

Monterey County Health Department

On 9/23/22, the United States had 33,238 documented new infections. There were also 259 deaths. Twenty-six states did not report their infections, and 30 states didn’t report their deaths. In the United States the number of hospitalized patients has decreased slightly in many areas and was 30,273 on September 24, a decrease of 6,417 hospitalizations compared to the previous 14 days. On 9/14/22 there are 3,176 patients who are seriously or critically ill; that number was 3,829 two weeks ago. The number of critically ill patients has decreased by 653 in the last 14 days, while at least 5,228 new deaths occurred. The number of critically ill patients has decreased for the fourth time in twenty-eight 14-day periods. Patients are still dying each day (average 375/day). Omicron BA.4, BA.4.6 and BA.5 variants are still causing infections. Past infections with a BA.1 or BA.2 variant will not prevent infections with BA.4, BA.4.6 or BA.5. Evusheld may not prevent BA.4.6 infections.

As of 9/23/22, we have had 1,081,566 deaths and 97,880,451 SARS-CoV-2 infections in the United States. We have had 854,450 new infections in the last 14 days. We are adding an average of 427,225 new infections every seven days. For the pandemic in the United States we are averaging one death for every 90.48 infections or over 11,050 deaths for each one million infections. As of 9/23/22, thirty-eight states have had greater than 500,000 total infections, and 38 states have had greater than 5,000 total deaths. Forty-six states have had greater than 2,000 deaths, and 43 states have greater than 2,000 deaths per million population. Vermont, at 1,152 deaths per million, and Hawaii, 1,186 deaths per million, are the states with the lowest death rates. Six states have over 4,000 deaths per million population: Mississippi (4,327), Arizona (4,304), Alabama (4,160), West Virginia (4,119), New Mexico (4,079) and Tennessee (4,057). Eighteen states (Alabama, Virginia, Missouri, North Carolina, Indiana, Tennessee, Massachusetts, Ohio, Michigan, Georgia, Illinois, New Jersey, Pennsylvania, Florida, Texas, New York, Arizona and California) have had greater than 20,000 deaths. Four states have had greater than 70,000 deaths: Florida (81,139 deaths), Texas (91,159 deaths), New York (72,058 deaths), and  California (95,970 deaths, 20th most deaths in the world). 

On 11/20/20, there were 260,331 (cumulative) deaths in the US from SARS-CoV-2. Since 11/20/20 (22 months), there were 820,435 new deaths from SARS-CoV-2. For eighteen of those months, vaccines have been available to all adults. During these eighteen months, 509,469 people have died of SARS-CoV-2 infections. Most of the hospitalizations and deaths could have been prevented by vaccination, proper masking, and social distancing. 

As of 9/23/22, California was ranked 32nd in the USA in infection percentage at 28.40%. In California, 24.43% of people were infected in the last 19 months. As of 9/23/22, 43 states have had greater than 25% of their population infected. No state has less than 20% of their population infected. Below are the variant proportions for Region 9, which includes California, Nevada, and Arizona. 

CDC

Worldwide, average deaths per day are 1,737 for the last 14 days, which is a 340 deaths-per-day decrease over the previous 14 days. The United States accounts for 21.58% (375 per day) of all deaths per day in the world over the last two weeks. Worldwide infections per day were 474,827. The United States accounts for 12.854% of those infections (or 61,032 infections per day). 

FDA-Approved Oral Drug Treatments for SARS-CoV-2

Pfizer has developed PAXLOVID™, an oral reversible inhibitor of C3-like protease of SARS-CoV-2. The drug inhibits this key enzyme that is crucial for virus production. The compound, also called Compound 6 (PF-07321332), is part of the drug combination PAXLOVID™ (PF-07321332; ritonavir), which just successfully completed a Phase 2-3 trial in humans in multiple countries. The preliminary results were announced on 11/5/21 by Pfizer. The results show that 89% of the hospitalizations and deaths were prevented in the drug treatment arm. The drug was administered twice a day for five days. No deaths occurred in the treatment group, and ten deaths occurred in the placebo group. The study was stopped by an independent data safety monitoring board, and the FDA concurred with this decision. Pfizer applied for an Emergency Use Authorization for this drug on 11/15/21. This drug was approved on 12/23/21. We have only been able to obtain PAXLOVID™ for two patients who we successfully treated with this drug obtained from CVS in Salinas (East Alisal Street; phone number 831-424-0026). They were expecting another shipment on 1/28/22. In my opinion, this agent, if more widely available, could markedly alter the course of every coronavirus infection throughout the world. 

Merck has developed the oral drug Molnupiravir, which induces RNA mutagenesis by viral RNA-dependent RNA polymerase of SARS-CoV-2 and other viruses. According to Kabinger et al, “Viral RNA-dependent RNA polymerase uses the active form of Molnupiravir, β-D-N4-hydroxycytidine triphosphate, as a substrate instead of cytidine triphosphate or uridine triphosphate. When the RNA-dependent RNA polymerase uses the resulting RNA as a template, β-D-N4-hydroxycytidine triphosphate directs incorporation of either guanine or adenine, leading to mutated (viral) RNA products. Analysis of RNA-dependent RNA polymerase–RNA complexes that contain mutagenesis products has demonstrated that β-D-N4-hydroxycytidine (the active form of Molnupiravir) can form stable base pairs with either guanine or adenine in RNA-dependent RNA polymerase explaining how the polymerase escapes proofreading and synthesizes mutated RNA” (quotation modified for clarity). The results of the phase 3 trial of Molnupiravir were published in the NEJM article “Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients” by Angélica Jayk Bernal, M.D. et al. (December 16, 2021 DOI: 10.1056/NEJMoa2116044). In this phase 3 study in the Molnupiravir group, 28 patients were hospitalized and one death occurred. In the placebo group, 53 patients were hospitalized and 9 died. Overall, 47% of hospitalizations and deaths were prevented by Molnupiravir. If you do a post hoc analysis and just look at deaths, Molnupiravir would prevent 89% of deaths. An Emergency Use Authorization by the FDA for Molnupiravir was approved on 12/24/21.The dose of Molnupiravir approved is four 200 mg capsules orally twice a day for five days. Diarrhea is reportedly a side effect in two percent of patients. I treated my first patient with Molnupiravir on 1/28/22. Currently more Molnupiravir is available weekly in the United States than PAXLOVID™ (see chart below; data from PHE.gov). Locally Molnupiravir is still available at CVS in Monterey (Fremont Blvd.; phone number: 831-375-5135) and CVS in Salinas (East Alisal Street; phone number 831-424-0026). 

FDA-Approved Intravenous Monoclonal Antibody Treatment for Non-Hospitalized SARS-CoV-2 Patients 

Bebtelovimab is a monoclonal antibody treatment for mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options approved or authorized by FDA are not accessible or clinically appropriate. The authorized dose of bebtelovimab is 175 mg, given as an intravenous injection over at least 30 seconds. The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for this drug on 2/11/22. Bebtelovimab is a human antibody that demonstrates neutralization against the Omicron variants and is available in every state and many hospitals and some clinics. If you are planning on using a monoclonal antibody to treat a SARS-CoV-2 infection, currently only bebtelovimab has activity against all Omicron variants, including BA.4.6. Researchers at Columbia University recently reported that “The loss of activity of tixagevimab and cilgavimab [components of Evusheld] against BA.4.6 leaves us with bebtelovimab as the only therapeutic mAb that has retained potent activity against all circulating forms of SARS-CoV-2.” For this reason, we no longer recommend Evusheld for immunocompromised patients with Omicron infections. 

An examination of the three variants that Wang et al identified as capable of immune escape in patients who receive the two monoclonal antibodies that are contained in Evusheld reveals that all three variants have a mutation in the spike protein at position 346. The changes substitute an uncharged amino acid— threonine (T), serine (S), or isoleucine (I)—for a positively-charged amino acid, arginine. This just goes to show that a single point mutation in the spike protein can render a monoclonal antibody treatment ineffective. Policy makers should keep in mind that the only way to prevent new drug-resistant variants like BA.4.6 from emerging is to prevent transmission of SARS-CoV-2 in the first place, using non-pharmaceutical interventions. The lack of use of N95 masks, with impending winter and influenza outbreaks, on top of COVID-19, is not wise public health and infectious disease policy. If we don’t make effective use of the non-pharmaceutical interventions available to us (masks, ventilation, social distancing), then the pharmaceutical interventions we have will all eventually be useless. 

Two virologists collaborated on Twitter to create the figure below, which Professor Johnson titled “Convergent Evolution on Steroids.”  It shows the key mutations present in many of the currently-circulating Omicron subvariants and demonstrates that mutation at site 346 is becoming more and more common. This means that even if prevalence of BA.4.6 wanes, we are still likely to have drug resistance issues with other newer variants. 

From Professor Marc Johnson, molecular virologist @SolidEvidence on Twitter and Daniele Focosi, M.D., Ph.D. @dfocosi on Twitter

Watching World Data

Over the next few months, we’ll be paying close attention to correlations between the SARS-CoV-2 data, the number of isolates identified in various countries and states, and the non-pharmaceutical interventions (like mask mandates and lockdowns) put in place by state and national governments. Data on infections, deaths, and percent of population infected was compiled from Worldometers. Data for this table for SARS-CoV-2 Isolates Currently Known in Location was compiled from GISAID and the CDC. It’s worth noting that GISAID provided more data than the CDC.

LocationTotal Infections as of 9/23/22New Infections on 9/23/22Total DeathsNew Deaths on 9/23/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World619,585,969(6,647,575  new infections in 14 days).410,5586,538,850(24,324 new deaths in last 14 days)1,3127.94%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617.2 (India)BV-1 (Texas, USA)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Theta/P.3 (Philippines) Mu/B.1.621 (Colombia)C.1.2 (South Africa 2% of isolates in July 2021)R1 (Japan)Omicron/B.1.1.529 + BA.1 + BA.2 + BA.3 (South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)Four new recombinants 12/31 to 3/22)BA.2.12.1 (USA)BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)  NoNo
USA97,880,451(ranked #1) 854,450 new infections in the last 14 days.
33,238(ranked #5)
26 states failed to report infections on 9/23/22.
1,081,566(ranked #1) 5,228 new deaths reported in the last 14 days. 259
30 states failed to report deaths on 9/23/22.
29.57%
B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan)         Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)Recombinant Delta AY.119.2- Omicron BA.1.1 (Tennessee, USA 12/31/21)\BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)NoNo
Brazil34,666,387(ranked #4) 129,467 new infections in the last 14 days. 6,861685,816(ranked #2; 950 new deaths in 14 days)9116.05%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)NoNo
India 44,563,337(ranked #2); 73,054 new infections in 2 weeks.4,912
528,487(ranked #3) 348 new deaths in 2 weeks.383.16%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)APTK India VOI 32421Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Iota/B.1.526 (USA-NYC) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India)NoNo
United Kingdom
23,621,952(ranked #7) 67,433 new infections in 2 weeks.189,919 (ranked #7) 893  new deaths in 2 weeks34.39%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)C.1.2 (South Africa)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)XD (AY.4/BA.1) recombinantXF (Delta/BA.1) recombinantXE (BA.1/BA.2) recombinantBA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)NoNo
California, USA11,228,790(ranked #14 in the world; 100,708 new infections in the last 14 days).1,61995,970 (ranked #20 in world)
616 new deaths in the last 14 days
1328.40%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)NoNo
Mexico7,080,152(ranked #18) 27,224 new infections in 14 days).4,147330,017(ranked #5)312 new deaths in 14 days)685.36%NoNo
South Africa4,017,163(ranked #37; 3,113 new infections in 14 days).152102,169 (ranked #18) 40 new deaths in 14 days)6.58%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)       C.1.2 (South Africa, July 2021)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)NoNo
Canada4,233,468(ranked #33) 35,767 new infections in 14 days).2,47744,992(ranked #24)
618new deaths in the last 14 days
3611.60% NoNo
Poland6,268,049 (ranked #21; 61,157 new infections in 14 days). 4,438117,431 (ranked #15)1916.60%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3 NoNo
Russia20,694,894(ranked #10), 734,599 new infections in 14 days).53,335 (ranked #2)386,551(ranked #4)1,386 new deaths in 14 days10414,16%NoNo
Peru4,140,129(ranked #34, 16,694 new infections in 14 days). 1,150216,446(ranked #6)1712.17%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Iran7,546,276(ranked #17; 8,495 new infections in last 14 days)421144,367(ranked #12)8.73%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)


NoNo
Spain13,393,196(ranked #12;   34,671 new infections in 14 days).-(ranked #18)113,845(ranked #16)676 new deaths in 14 days28.61%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
France35,050,133 (ranked #3; 367,940 new infections in the last 14 days).38,464 (ranked #6)154,854 (ranked #10)
386  new deaths in 14 days
3053.44%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinantNoNo
Germany32,905,086(ranked #5; 452,824 new infections in 14 days.).50,800 (ranked #3)149,368 (ranked #11)
1,139  new deaths in 14 days
9339.22%
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
South Korea24,535,940 (ranked #6 601,906 new infections in 14 days).39,972(ranked #8)28,009 (ranked #37) 
628 new deaths in 14 days
5947.80%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Vietnam11,467,619 (ranked #13; 32,147 new infections in 14 days).1,92843,146 (ranked #26)11.58%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Netherlands8,413,532 (ranked #16; 16,553 new infections in 14 days).1,75622,633 (ranked #41)148.98%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
Denmark3,097,088 (ranked #40) 7,517 new infections in 14 days6407,021 (ranked #79)53.22%53.07%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo




Taiwan6,132,744(ranked #22)
518,546 new infections in 14 days
42,420 (ranked #4)10,702 (ranked #63)
5925.67%
2.17% of population has been infected in the last 14 days
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Japan20,840,785(ranked #9)
958,392 new infections in the last 14 days
61,478(ranked #1)44,071(ranked #25)
1,970 new deaths in the last 14 days
12016.59%
0.76% of population has been infected in the last 14 days
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)BA.2*BA.5*NoNo

What Our Team Is Reading This Week

COVID-19

SARS-CoV-2 Update

It’s time for our next 14-day moving average determinations for SARS-CoV-2 for the United States and my thoughts on vaccines, SARS-CoV-2 therapeutic agents and mutant viruses. We use the WORLDOMETERS aggregators data set to make any projections since it includes data from the Department of Veterans Affairs, the U.S. Military, federal prisons and the Navajo Nation.

SARS-CoV-2 infections per day in the United States have decreased for the first time in two weeks; however, there is still widespread underreporting by states, a failure to capture positive home tests, and a decreased PCR screening program in most states. Deaths per day had been decelerating at a rapid rate in the United States but are now increased by 57 more deaths per day. The number of infections have increased as the Omicron BA.2.12.1, BA.2, BA.4, and BA.5 variants of SARS CoV-2 have spread across the nation. The CDC estimates that BA.2.12.1 accounted for 0.8% of isolates, BA.2 accounted for 0%, BA.5 accounted for 88.8%, BA.4 accounted for 5.3%, BA.4.6 accounted for 5.1%, and B.1.1.529 accounted for 0% in the week ending August 13.

CDC

We frequently hear messaging from health officials and politicians that Omicron is “mild,” especially compared to the Delta variant, and as a result, many of our patients believe that they no longer need to wear their masks. This is a dangerous misconception. SARS-CoV-2 still remains a highly transmissible, airborne virus. The following graph, based on CDC data from April 2, 2022, shows that Omicron deaths in people over 65 are much higher than Delta deaths in the same age group. In fact, the peak of Omicron deaths in people over 65 years of age is 163% higher than the Delta peak. The death rate from Omicron is only lower than Delta in the populations between 12 and 64 years of age. Until we have more data on these newer mutants of SARS-CoV-2, we will not know the lethality of each variant. It may take months to measure objective differences in the death rates of new circulating variants. We recommend that all of our patients and family members continue to wear N95 masks in all enclosed spaces.

In patients treated with Paxlovid for five days who have persistent symptoms and continued positivity, we feel that clinicians should consider giving a second course of Paxlovid for five days. Boucau et al have demonstrated that in a study of seven patients with recurrent symptoms, “High viral loads (median 6.1 log10 copies/mL) were detected after rebound for a median of 17 days after initial diagnosis. Three had culturable virus for up to 16 days after initial diagnosis.” This was not due to resistance-associated mutations of the virus, suggesting that the course of therapy may be inadequate in this group of persistently infected patients. 

NY Times

The Omicron variant has continued to mutate just like Delta. There are now 230 Omicron sub-variants (an unexplained decrease of 9 in the last two weeks) that have been assigned Pango lineages, including 116 sub-lineages of BA.2 (no increase in two weeks), one sub-lineage of BA.3, 14 sub-lineages of BA.4 (no increase in two weeks), and 24 sub-lineages of BA.5 (no increase in two weeks). The BF lineage (new eight weeks ago) now has 11 sublineages, no increase in two weeks. The BE lineage (also new eight weeks ago), with BE.1 first detected in South Africa, Austria and England, still has 4 sublineages. There are also new lineages from eight weeks ago: BC.1 (Japan), BC.2 (Peru),BD.1 (UK), BG.1 (Peru), BG.2 (US, Denmark, Canada), BG.3 (Peru), BG.4 (Israel). 

Omicron variants have mutations which decrease the effectiveness of current vaccines and monoclonal antibodies. The effectiveness of the new Pfizer drug, PAXLOVIDTM, should not be compromised by any of the current mutations in Omicron or Delta variants. Pfizer completed their filing with the FDA on 11/15/21. The FDA approved PAXLOVIDTM on December 22 , 2021.The FDA approved Merck’s drug Molnupiravir on December 23, 2021. On 12/23/21 CVS announced by fax it was selected by the Government to distribute oral PAXLOVIDTM and Molnupiravir. On 12/27/21, another fax from CVS listed which CVS pharmacies in California would have these drugs. Monterey County covers 3,771 square miles with a population of 434,061. Three CVS pharmacies in Monterey, Salinas, and Soledad are the only listed pharmacies in our county. I have now been able to obtain PAXLOVIDTM for infected patients from the CVS in Salinas (phone 831-424-0026), the CVS on Fremont Street in Monterey (phone 831-375-5135) and the CVS in Soledad in south Monterey County (phone 831-678-5110). All require electronic prescriptions written as Paxlovid three tablets twice daily orally for five days (thirty total tablets).  Physicians or their staff probably should call to check on drug availability that day.

In the absence of obtaining intravenous Sotrovimab or Bebtelovimab, only oral PAXLOVIDTM and Molnupiravir are available to treat SARS-CoV-2 as an outpatient. Our first Paxlovid failure in an immunocompromised patient was treated the week of 4/5/22 at the Community Hospital of the Monterey Peninsula (Montage) ER as an outpatient with a single one-minute intravenous injection of Bebtelovimab. 

In Monterey County, as of 8/14/22, 0.3% of 0-4 year-olds and 38.9% of 5-11 year-olds have received the first two doses of vaccine, while 72.8% of 12-17 year-olds have received two doses. Only 53.3% of Monterey County residents have received a third dose of the vaccine. On June 17, The FDA authorized both the Pfizer and Moderna vaccines for use in children ages 6 months to four years. We believe children under 5 should be vaccinated as soon as possible. We would anticipate, with the start of school on August 5 and the low vaccination rates in our county, that we’ll have a marked increase in the number of infected patients. All Monterey County residents should get up to date on COVID-19 vaccinations as soon as possible. 

Monterey County Public Health

FDA Approved Intramuscular Prophylaxis of SARS-CoV-2 Immunocompromised Patients

Evusheld (from AstraZeneca) contains two human monoclonal antibodies, Tixagevimab (150 mg in 1.5 mL) and Cilgavimab (150 mg in 1.5 mL), in separate vials. According to the manufacturer, “Tixagevimab and Cilgavimab are two recombinant human IgG1κ monoclonal antibodies with amino acid substitutions to extend antibody half-life (YTE), reduce antibody effector function, and minimize the potential risk of antibody-dependent enhancement of disease (TM). Tixagevimab and Cilgavimab can simultaneously bind to non-overlapping regions of the receptor binding domain (RBD) of SARS-CoV-2 spike protein. Tixagevimab, Cilgavimab, and their combination bind to spike protein with equilibrium dissociation constants of KD = 2.76 pM, 13.0 pM and 13.7 pM, respectively, blocking its interaction with human ACE2, the SARS-CoV-2 receptor, which is required for virus attachment. Tixagevimab, Cilgavimab, and their combination blocked RBD binding to human ACE2 with IC50 values of 0.32 nM (48 ng/mL), 0.53 nM (80 ng/mL), and 0.43 nM (65 ng/mL), respectively.” Each monoclonal antibody is administered intramuscularly to immunocompromised patients in two separate injections every six months. Evusheld availability in California is limited and has been rationed/distributed by our local Public Health Department only to hospitals. Physicians in Monterey County who want to receive a distribution (or redistribution) of Evusheld need to be added to the list of eligible facilities by the State Therapeutics group. The first step is for the Monterey County EMS Agency (phone: 831-755-5713) to make a request to the State Therapeutics group to have the facility added to the system for further verification.  Due to extremely limited availability, evidently the State Therapeutics group is currently only considering additions on a case by case basis.  Physicians who wish to submit their facility for consideration will need to provide the following information to the Monterey County EMS Agency:

  1. Facility/Provider Name for Registration
  2. Provider Type (Hospital, Pharmacy, Etc)
  3. Shipping Address
  4. Contact Name(s)
  5. Contact Email(s)
  6. Contact Phone Number(s)

As for my immunocompromised patients: We provided this information by email to the Monterey County EMS Agency on 1/26/22 and will update you when or if we become an eligible provider and receive our first doses of Evusheld. 

Watching World Data

Over the next few months, we’ll be paying close attention to correlations between the SARS-CoV-2 data, the number of isolates identified in various countries and states, and the non-pharmaceutical interventions (like mask mandates and lockdowns) put in place by state and national governments. Data on infections, deaths, and percent of population infected was compiled from Worldometers. Data for this table for SARS-CoV-2 Isolates Currently Known in Location was compiled from GISAID and the CDC. It’s worth noting that GISAID provided more data than the CDC.

LocationTotal Infections as of 8/12/22New Infections on 8/12/22Total DeathsNew Deaths on 8/12/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World593,948,648(13,178,472 new infections in 14 days).792,5726,451,858(34,360 new deaths in last 14 days)2,2417.61%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617.2 (India)BV-1 (Texas, USA)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Theta/P.3 (Philippines) Mu/B.1.621 (Colombia)C.1.2 (South Africa 2% of isolates in July 2021)R1 (Japan)Omicron/B.1.1.529 + BA.1 + BA.2 + BA.3 (South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)Four new recombinants 12/31 to 3/22)BA.2.12.1 (USA)BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)NoNo
USA94,643,632(ranked #1) 1,589,448 new infections in the last 14 days.
85,116(ranked #3)
22 states failed to report infections on 8/12/22.
1,062,151(ranked #1) 7,131  new deaths reported in the last 14 days. 335
28 states failed to report deaths on 8/12/22..
26.72%*
*Not updated for 6 weeks by Worldometer.
B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan)         Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)Recombinant Delta AY.119.2- Omicron BA.1.1 (Tennessee, USA 12/31/21)\BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)BA.4.6 (USA 7/22)NoNo
Brazil34,148,131(ranked #3) 352,939 new infections in the last 14 days. 23,552 (ranked #7)681,317(ranked #2; 2,942 new deaths in 14 days)29215.82%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)NoNo
India 44,239.372(ranked #2); 239,234 new infections in 2 weeks.15,815 (ranked#11)
526,966(ranked #3) 654 new deaths in 2 weeks.683.14%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)APTK India VOI 32421Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Iota/B.1.526 (USA-NYC) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India)NoNo
United Kingdom*
*No reported data for 8/12/22
23,420,826(ranked #6) 116,347 new infections in 2 weeks.186,087 (ranked #7) 2,134 new deaths in 2 weeks34.12%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)C.1.2 (South Africa)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)XD (AY.4/BA.1) recombinantXF (Delta/BA.1) recombinantXE (BA.1/BA.2) recombinantBA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)NoNo
California, USA10,896,796(ranked #14 in the world;  198618 new infections in the last 14 days).13,30694,319 (ranked #20 in world)
615 new deaths in the last 14 days
5027.57%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)BA.2.75 (India 7/22)NoNo
Mexico6,903,862(ranked #18) 192,015 new infections in 14 days).13,313(ranked #12)328,596(ranked #5)1,071 new deaths in 214 days)715.23%B2 lineageAlpha/B.1.1.7 (UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
South Africa4,007,925(ranked #33; 3,370 new infections in 14 days).313101,982 (ranked #18) Not updated in last 2 weeks.6.58%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)       C.1.2 (South Africa, July 2021)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2BA.4 (South Africa 11/21)BA.5 (South Africa 11/21)NoNo
Canada4,109,931(ranked #33) 87,572 new infections in 14 days).3,60343,583(ranked #24)3710.69% B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
Poland6,113,840 (ranked #21; 48,508 new infections in 14 days). 4,223116,751 (ranked #15)1416.19%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3 NoNo
Russia18,824,282(ranked #9), 247,309 new infections in 14 days).27,810383,011(ranked #4 in world)5712.88%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)R1 (Japan) B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Peru4,013,831(ranked #34, 118,345 new infections in 14 days). 10,882214,890(ranked #6)7211.82%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Iran7,465,579(ranked #17; 88,785 new infections in last 14 days)6,404142,806(ranked #12)548.65%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)


NoNo
Spain13,294,139(ranked #12;   67,560 new infections in 14 days).4,528(ranked #22)111,667 (ranked #16)11028.41%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
France34,191,919 (ranked #3; 405,153 new infections in the last 14 days).22,638 (ranked #9)153,064 (ranked #10)
1,101 new deaths in 14 days
7452.13%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinantNoNo
Germany31,535,343(ranked #5; 682,031 new infections in 14 days.).45,859 (ranked #4)145,698 (ranked #11)
1,726 new deaths in 14 days
13737.38%
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
South Korea21,111,840 (ranked #8 1,491,323 new infections in 14 days).128,671(ranked #2)25,499 (ranked #37) 5841.10%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Vietnam11,362,540 (ranked #13; 586,056 new infections in 14 days).2,19243,096 (ranked #25)111.45%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Netherlands8,362,564 (ranked #16; 31,241 new infections in 14 days).1,88222,542 (ranked #41)448.57%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
Denmark3,076,642 (ranked #40) 16,658 new infections in 14 days1,3236,792 (ranked #80)1252.72%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo




Taiwan4,846,477(ranked #24)
300,841 new infections in 14 days
21,965 (ranked #10)9,373 (ranked #67)
3120.27%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Japan15,086,304(ranked #11)
2,908,192 new infections in the last 14 days
224,929(ranked #1)34,537(ranked #30)
2,251 new deaths in the last 14 days
21412.00%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)BA.2*BA.5*NoNo

What Our Team Is Reading This Week

COVID-19

SARS-CoV-2 Update

It’s time for our next 14-day moving average determinations for SARS-CoV-2 for the United States and my thoughts on vaccines, SARS-CoV-2 therapeutic agents and mutant viruses. We use the WORLDOMETERS aggregators data set to make any projections since it includes data from the Department of Veterans Affairs, the U.S. Military, federal prisons and the Navajo Nation.

SARS-CoV-2 infections per day have been increasing in the United States for 16 consecutive weeks despite underreporting by states and the failure to capture positive home tests and a decreased screening program in most states. Deaths per day had been decelerating at a rapid rate in the United States but are now increased by 65 more deaths per day. The number of infections have increased as the Omicron BA.2.12.1, BA.2, BA.4, and BA.5 variants of SARS CoV-2 have spread across the nation. The CDC estimates that BA.2.12.1 accounted for 5.0% of isolates, BA.2 accounted for 0.3%, BA.5 accounted for 89.1%, BA.4 accounted for 12.9%, and B.1.1.529 accounted for 0% in the week ending July 23.

CDC

We frequently hear messaging from health officials and politicians that Omicron is “mild,” especially compared to the Delta variant, and as a result, many of our patients believe that they no longer need to wear their masks. This is a dangerous misconception. SARS-CoV-2 still remains a highly transmissible, airborne virus. The following graph, based on CDC data from April 2, 2022, shows that Omicron deaths in people over 65 are much higher than Delta deaths in the same age group. In fact, the peak of Omicron deaths in people over 65 years of age is 163% higher than the Delta peak. The death rate from Omicron is only lower than Delta in the populations between 12 and 64 years of age. Until we have more data on these newer mutants of SARS-CoV-2, we will not know the lethality of each variant. It may take months to measure objective differences in the death rates of new circulating variants. We recommend that all of our patients and family members continue to wear N95 masks in all enclosed spaces.

In patients treated with Paxlovid for five days who have persistent symptoms and continued positivity, we feel that clinicians should consider giving a second course of Paxlovid for five days. Boucau et al have demonstrated that in a study of seven patients with recurrent symptoms, “High viral loads (median 6.1 log10 copies/mL) were detected after rebound for a median of 17 days after initial diagnosis. Three had culturable virus for up to 16 days after initial diagnosis.” This was not due to resistance-associated mutations of the virus, suggesting that the course of therapy may be inadequate in this group of persistently infected patients. 

NY Times

The Omicron variant has continued to mutate just like Delta. There are now 239 Omicron sub-variants (an increase of 28 in the last two weeks) that have been assigned Pango lineages, including 116 sub-lineages of BA.2 (an increase of 4 in two weeks), one sub-lineage of BA.3, 14 sub-lineages of BA.4 (an increase of 3 in two weeks), and 24 sub-lineages of BA.5 (an increase of 7 in two weeks). The BF lineage (new six weeks ago) now has 11 sublineages, an increase of 5 in two weeks. The BE lineage (also new six weeks ago), with BE.1 first detected in South Africa, Austria and England, still has 4 sublineages. There are also new lineages from six weeks ago: BC.1 (Japan), BC.2 (Peru), BD.1 (UK), BG.1 (Peru), BG.2 (US, Denmark, Canada), BG.3 (Peru), BG.4 (Israel).

Unless people continue to wear masks and get vaccinated, including their third dose of the vaccine, we will see further spread of the Omicron variants and increase in deaths in people who are not vaccinated, those who have waning immunity, the immunocompromised population, and others with risk factors, particularly those older over the age of 64. SARS-CoV-2 is now in the top ten most common causes of death for children. Anyone over the age of 5 years can now get vaccinated in the United States at no cost. This should get done immediately. 

In Monterey County, as of 7/31/22, 0.1% of 0-4 year-olds and 38.6% of 5-11 year-olds have received the first two doses of vaccine, while 72.6% of 12-17 year-olds have received two doses. Only 53.2% of Monterey County residents have received a third dose of the vaccine. On June 17, The FDA authorized both the Pfizer and Moderna vaccines for use in children ages 6 months to four years. We believe children under 5 should be vaccinated as soon as possible. We would anticipate, with the start of school on August 5 and the low vaccination rates in our county, that we’ll have a marked increase in the number of infected patients. All Monterey County residents should get up to date on COVID-19 vaccinations as soon as possible. 

Monterey County Health Department
Monterey County Health Department

On 7/29/22, the United States had 99,061 documented new infections. There were also 286 deaths. Twenty-two states did not report their infections, and 28 states didn’t report their deaths. In the United States the number of hospitalized patients has been increasing in many areas and was 44,207 on July 29, an increase of 9% compared to the previous 14 days. Now there are 4,723 patients who are seriously or critically ill; that number was 4,180 two weeks ago. The number of critically ill patients has increased by 543 in the last 14 days, while at least 6,327 new deaths occurred (an increase of 65 deaths per day from the previous 14 days). The number of critically ill patients has increased for the seventh time in twenty-four 14-day periods. Patients are still dying each day (average 387/day). Omicron BA.2, BA.2.12.1, BA.4, and BA.5 variants causing infections should continue to increase and critically ill patients may continue to increase. Deaths, which usually lag two to four weeks behind exponential increase in infections, are increasing now. Past infections with a BA.1 or BA.2 variant will not prevent infections with BA.2.12.1, BA.4, or BA.5. 

As of 7/29/22, we have had 1,055,020 deaths and 93,054,184 SARS-CoV-2 infections in the United States. We have had 1,883,613 new infections in the last 14 days. We are adding an average of 941,807 infections every seven days. For the pandemic in the United States we are averaging one death for every 88.20 infections or over 11,338 deaths for each one million infections. As of 7/29/22, thirty-eight states have had greater than 500,000 total infections, and 37 states have had greater than 5,000 total deaths. Seventeen states (Virginia, Missouri, North Carolina, Indiana, Tennessee, Massachusetts, Ohio, Michigan, Georgia, Illinois, New Jersey, Pennsylvania, Florida, Texas, New York, Arizona and California) have had greater than 20,000 deaths. Four states (Florida, Texas, New York, and California) have had greater than 70,000 deaths. California and Texas have each had greater than 89,000 deaths with California having 93,704 deaths (20th most deaths in the world). 

As of 7/1/22, in the United States, 26.72% of the population has had a documented SARS-CoV-2 infection. In the 18 months preceding 7/1/22, 23.97% of our country became infected with SARS-CoV-2. On 11/20/20, there were 260,331 (cumulative) deaths in the US from SARS-CoV-2. 

In the last 18 months, there were 794,889 new deaths from SARS-CoV-2. For fifteen of those months, vaccines have been available to all adults. During these fifteen months, 483,923 people have died of SARS-CoV-2 infections. Most of the hospitalizations and deaths could have been prevented by vaccination, proper masking, and social distancing. 

As of 7/29/22, California was ranked 32th in the USA in infection percentage at 27.07%. In California, 23.1% of people were infected in the last 18 months. As of 7/29/22, 38 states have had greater than 25% of their population infected. 

Worldwide, average deaths per day are 2,263 for the last 14 days, which is a 417 deaths-per-day increase over the previous 14 days. The United States accounts for 19.97% (452 per day) of all deaths per day in the world over the last two weeks. Worldwide infections per day were 1,030,492. The United States accounts for 13.06% of those infections (or 134,544 infections per day). 

FDA-Approved Oral Drug Treatments for SARS-CoV-2

Pfizer has developed PAXLOVID™, an oral reversible inhibitor of C3-like protease of SARS-CoV-2. The drug inhibits this key enzyme that is crucial for virus production. The compound, also called Compound 6 (PF-07321332), is part of the drug combination PAXLOVID™ (PF-07321332; ritonavir), which just successfully completed a Phase 2-3 trial in humans in multiple countries. The preliminary results were announced on 11/5/21 by Pfizer. The results show that 89% of the hospitalizations and deaths were prevented in the drug treatment arm. The drug was administered twice a day for five days. No deaths occurred in the treatment group, and ten deaths occurred in the placebo group. The study was stopped by an independent data safety monitoring board, and the FDA concurred with this decision. Pfizer applied for an Emergency Use Authorization for this drug on 11/15/21. This drug was approved on 12/23/21. We have only been able to obtain PAXLOVID™ for two patients who we successfully treated with this drug obtained from CVS in Salinas (East Alisal Street; phone number 831-424-0026). They were expecting another shipment on 1/28/22. In my opinion, this agent, if more widely available, could markedly alter the course of every coronavirus infection throughout the world. 

Merck has developed the oral drug Molnupiravir, which induces RNA mutagenesis by viral RNA-dependent RNA polymerase of SARS-CoV-2 and other viruses. According to Kabinger et al, “Viral RNA-dependent RNA polymerase uses the active form of Molnupiravir, β-D-N4-hydroxycytidine triphosphate, as a substrate instead of cytidine triphosphate or uridine triphosphate. When the RNA-dependent RNA polymerase uses the resulting RNA as a template, β-D-N4-hydroxycytidine triphosphate directs incorporation of either guanine or adenine, leading to mutated (viral) RNA products. Analysis of RNA-dependent RNA polymerase–RNA complexes that contain mutagenesis products has demonstrated that β-D-N4-hydroxycytidine (the active form of Molnupiravir) can form stable base pairs with either guanine or adenine in RNA-dependent RNA polymerase explaining how the polymerase escapes proofreading and synthesizes mutated RNA” (quotation modified for clarity). The results of the phase 3 trial of Molnupiravir were published in the NEJM article “Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients” by Angélica Jayk Bernal, M.D. et al. (December 16, 2021 DOI: 10.1056/NEJMoa2116044). In this phase 3 study in the Molnupiravir group, 28 patients were hospitalized and one death occurred. In the placebo group, 53 patients were hospitalized and 9 died. Overall, 47% of hospitalizations and deaths were prevented by Molnupiravir. If you do a post hoc analysis and just look at deaths, Molnupiravir would prevent 89% of deaths. An Emergency Use Authorization by the FDA for Molnupiravir was approved on 12/24/21.The dose of Molnupiravir approved is four 200 mg capsules orally twice a day for five days. Diarrhea is reportedly a side effect in two percent of patients. I treated my first patient with Molnupiravir on 1/28/22. Currently more Molnupiravir is available weekly in the United States than PAXLOVID™ (see chart below; data from PHE.gov). Locally Molnupiravir is still available at CVS in Monterey (Fremont Blvd.; phone number: 831-375-5135) and CVS in Salinas (East Alisal Street; phone number 831-424-0026). 

FDA Approved Intramuscular Prophylaxis of SARS-CoV-2 Immunocompromised Patients

Evusheld (from AstraZeneca) contains two human monoclonal antibodies, Tixagevimab (150 mg in 1.5 mL) and Cilgavimab (150 mg in 1.5 mL), in separate vials. According to the manufacturer, “Tixagevimab and Cilgavimab are two recombinant human IgG1κ monoclonal antibodies with amino acid substitutions to extend antibody half-life (YTE), reduce antibody effector function, and minimize the potential risk of antibody-dependent enhancement of disease (TM). Tixagevimab and Cilgavimab can simultaneously bind to non-overlapping regions of the receptor binding domain (RBD) of SARS-CoV-2 spike protein. Tixagevimab, Cilgavimab, and their combination bind to spike protein with equilibrium dissociation constants of KD = 2.76 pM, 13.0 pM and 13.7 pM, respectively, blocking its interaction with human ACE2, the SARS-CoV-2 receptor, which is required for virus attachment. Tixagevimab, Cilgavimab, and their combination blocked RBD binding to human ACE2 with IC50 values of 0.32 nM (48 ng/mL), 0.53 nM (80 ng/mL), and 0.43 nM (65 ng/mL), respectively.” Each monoclonal antibody is administered intramuscularly to immunocompromised patients in two separate injections every six months. Evusheld availability in California is limited and has been rationed/distributed by our local Public Health Department only to hospitals. Physicians in Monterey County who want to receive a distribution (or redistribution) of Evusheld need to be added to the list of eligible facilities by the State Therapeutics group. The first step is for the Monterey County EMS Agency (phone: 831-755-5713) to make a request to the State Therapeutics group to have the facility added to the system for further verification.  Due to extremely limited availability, evidently the State Therapeutics group is currently only considering additions on a case by case basis.  Physicians who wish to submit their facility for consideration will need to provide the following information to the Monterey County EMS Agency:

  1. Facility/Provider Name for Registration
  2. Provider Type (Hospital, Pharmacy, Etc)
  3. Shipping Address
  4. Contact Name(s)
  5. Contact Email(s)
  6. Contact Phone Number(s)

As for my immunocompromised patients: We provided this information by email to the Monterey County EMS Agency on 1/26/22 and will update you when or if we become an eligible provider and receive our first doses of Evusheld. 

On 2/24/22, the FDA revised its dosing guidance for Evusheld, doubling the dosage of its two components, Tixagevimab and Cilgavimab, from 150 mg each to 300 mg each. They explain, “Based on the most recent information and data available, Evusheld may be less active against certain Omicron subvariants. The dosing regimen was revised because available data indicate that a higher dose of Evusheld may be more likely to prevent infection by the COVID-19 Omicron subvariants BA.1 and BA.1.1 than the originally authorized Evusheld dose.” Patients who have already received their first administration of Evusheld intramuscularly will need to contact their healthcare provider to get a second 150 mg injection of Tixagevimab and Cilgavimab. If you have not received Evusheld yet, the correct dose is 3 mL/300 mg of each monoclonal antibody injected intramuscularly. This large volume necessitates administration of the antibodies in the gluteus, with two separate injections. 

Watching World Data

Over the next few months, we’ll be paying close attention to correlations between the SARS-CoV-2 data, the number of isolates identified in various countries and states, and the non-pharmaceutical interventions (like mask mandates and lockdowns) put in place by state and national governments. Data on infections, deaths, and percent of population infected was compiled from Worldometers. Data for this table for SARS-CoV-2 Isolates Currently Known in Location was compiled from GISAID and the CDC. It’s worth noting that GISAID provided more data than the CDC.

LocationTotal Infections as of 7/29/22New Infections on 7/29/22Total DeathsNew Deaths on 7/29/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World580,770,176(14,426,888 new infections in 14 days).905,4056,417,498(31,678 new deaths in last 14 days)2,8087.45%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617.2 (India)BV-1 (Texas, USA)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Theta/P.3 (Philippines) Mu/B.1.621 (Colombia)C.1.2 (South Africa 2% of isolates in July 2021)R1 (Japan)Omicron/B.1.1.529 + BA.1 + BA.2 + BA.3 (South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)Four new recombinants 12/31 to 3/22)BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)NoNo
USA93,054,184(ranked #1) 1,883,613 new infections in the last 14 days.
99,081(ranked #4)
22 states failed to report infections.
1,055,020(ranked #1) 6,327 new deaths in the last 14 days. 28628 states failed to report deaths.26.72%*
*Not updated for four weeks by Worldometers
B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan)         Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)Recombinant Delta AY.119.2- Omicron BA.1.1 (Tennessee, USA 12/31/21)\BA.2BA.2.12.1 (United States)BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India)NoNo
Brazil33,795,192(ranked #3) 545,075 new infections in the last 14 days. 42,816 (ranked #8)678,375(ranked #2; 3,230 new deaths in 14 days)22815.66%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
India 44,000,138(ranked #2); 270,067 new infections in 2 weeks.20,408
526,312(ranked #3)543.12%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)APTK India VOI 32421Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Iota/B.1.526 (USA-NYC) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2.75 (India)NoNo
United Kingdom*
*No reported data for 7/29/22
23,304,479(ranked #6) 229,119 new infections in 2 weeks.183,953 (ranked #7) 
2,373 new deaths in 2 weeks
33.95%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)C.1.2 (South Africa)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)XD (AY.4/BA.1) recombinantXF (Delta/BA.1) recombinantXE (BA.1/BA.2) recombinantBA.2BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India)NoNo
California, USA10,698,178(ranked #14 in the world;  317,309 new infections in the last 14 days).18,71593,704 (ranked #20 in world)
687 new deaths in the last 14 days
5127.07%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa)BA.5 (South Africa)NoNo
Mexico6,711,847(ranked #18) 337,971 new infections in 14 days).24,893(ranked #9)327,525(ranked #5)1135.09%B2 lineageAlpha/B.1.1.7 (UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
South Africa4,004,555(ranked #33; 4,704 new infections in 14 days).354101,982 (ranked #18)56.58%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)       C.1.2 (South Africa, July 2021)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)NoNo
Canada4,012,359(ranked #32) 4,896 new infections in 14 days).43,583(ranked #24)10.44% .B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
Poland6,065,332 (ranked #21; 35,385 new infections in 14 days). 3,391116,556 (ranked #15)916.06%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3 NoNo
Russia18,576,973(ranked #9), 96,039 new infections in 14 days).11,422382,352(ranked #4 in world)3912.71%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)R1 (Japan) B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Peru3,895,486(ranked #37, 181,125 new infections in 14 days). 6,467214,195(ranked #6)4111.48%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Iran7,376,794(ranked 17th; 106,771 new infections in last 14 days)7,849141,891(ranked #12)548.55%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)


NoNo
Spain13,226,579(ranked 11th;   136,103 new infections in 14 days).7,783(ranked #18)110,719 (ranked #16)10928.26%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
France33,786,766 (ranked #4; 967,865 new infections in the last 14 days).45,515 (ranked #6)151,983 (ranked #10)
1,407 new deaths in 14 days
8951.52%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinantNoNo
Germany30,853,312(ranked #5; 1,170,323 new infections in 14 days.).66,003 (ranked #4)143,972 (ranked #11)
1,437 new deaths in 14 days
11736.58%
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
South Korea19,620,517 (ranked #9 940,375 new infections in 14 days).85,275(ranked #3)24,999 (ranked #38) 3538.20%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Vietnam10,776,484 (ranked #13; 17,339 new infections in 14 days).1,80343,093 (ranked #25)110.86%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Netherlands8,331,315 (ranked #18; 57,081 new infections in 14 days).3,23822,492 (ranked #41)448.40%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
Denmark3,059,984 (ranked #39) 20,125 new infections in 14 days1,0376,639 (ranked #81)1152.44%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo




Taiwan4,545,636(ranked #29)
330,436 new infections in 14 days
23,289 (ranked #10)8,833 (ranked #69)
916 new deaths in 14 days
5719.01%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Japan12,118,112(ranked #12)
2,117,392 new infections in the last 14 days
230,055(ranked #1)32,286(ranked #30)1169.64%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo

What Our Team Is Reading This Week

COVID-19

SARS-CoV-2 Update

It’s time for our next 14-day moving average determinations for SARS-CoV-2 for the United States and my thoughts on vaccines, SARS-CoV-2 therapeutic agents and mutant viruses. We use the WORLDOMETERS aggregators data set to make any projections since it includes data from the Department of Veterans Affairs, the U.S. Military, federal prisons and the Navajo Nation.

SARS-CoV-2 infections per day have been increasing in the United States for 14 consecutive weeks despite underreporting by states and the failure to capture positive home tests and a decreased screening program in most states. Deaths per day had been decelerating at a rapid rate in the United States but are now increased by 29 more deaths per day. The number of infections have increased as the Omicron BA.2.12.1, BA.2, BA.4, and BA.5 variants of SARS CoV-2 have spread across the nation. The CDC estimates that BA.2.12.1 accounted for 17.3% of isolates, BA.2 accounted for 1.4%, BA.5 accounted for 65.0%, BA.4 accounted for 16.3%, and B.1.1.529 accounted for 0% in the week ending June 25.

CDC

We frequently hear messaging from health officials and politicians that Omicron is “mild,” especially compared to the Delta variant, and as a result, many of our patients believe that they no longer need to wear their masks. This is a dangerous misconception. SARS-CoV-2 still remains a highly transmissible, airborne virus. The following graph, based on CDC data from April 2, 2022, shows that Omicron deaths in people over 65 are much higher than Delta deaths in the same age group. In fact, the peak of Omicron deaths in people over 65 years of age is 163% higher than the Delta peak. The death rate from Omicron is only lower than Delta in the populations between 12 and 64 years of age. Until we have more data on these newer mutants of SARS-CoV-2, we will not know the lethality of each variant. It may take months to measure objective differences in the death rates of new circulating variants. We recommend that all of our patients and family members continue to wear N95 masks in all enclosed spaces.

NY Times

In patients treated with Paxlovid for five days who have persistent symptoms and continued positivity, we feel that clinicians should consider giving a second course of Paxlovid for five days. Boucau et al have demonstrated that in a study of seven patients with recurrent symptoms, “High viral loads (median 6.1 log10 copies/mL) were detected after rebound for a median of 17 days after initial diagnosis. Three had culturable virus for up to 16 days after initial diagnosis.” This was not due to resistance-associated mutations of the virus, suggesting that the course of therapy may be inadequate in this group of persistently infected patients. 

The Omicron variant has continued to mutate just like Delta. There are now 211 Omicron sub-variants (an increase of 12 in the last two weeks) that have been assigned Pango lineages, including 112 sub-lineages of BA.2 (an increase of 8 in two weeks), one sub-lineage of BA.3, 11 sub-lineages of BA.4 (an increase of 2 in two weeks), and 17 sub-lineages of BA.5 (an increase of 2 in two weeks). The BF lineage (new four weeks ago), with BF.1 first detected in England, Denmark, Spain and Scotland still has 6 sublineages. The BE lineage (also new four weeks ago), with BE.1 first detected in South Africa, Austria and England, now has 4 sublineages (one new in the past two weeks). There are also new lineages from four weeks ago: BC.1 (Japan), BC.2 (Peru),BD.1 (UK), BG.1 (Peru), BG.2 (US, Denmark, Canada), BG.3 (Peru), BG.4 (Israel). 

Unless people continue to wear masks and get vaccinated, including their third dose of the vaccine, we will see further spread of the Omicron variants and increase in deaths in people who are not vaccinated, those who have waning immunity, the immunocompromised population, and others with risk factors, particularly those older over the age of 64. SARS-CoV-2 is now in the top ten most common causes of death for children. Anyone over the age of 5 years can now get vaccinated in the United States at no cost. This should get done immediately.

In Monterey County, as of 7/17/22, 0.0% of 0-4 year-olds and 38.3% of 5-11 year-olds have received the first two doses of vaccine, while 72.4% of 12-17 year-olds have received two doses. Only 53% of Monterey County residents have received a third dose of the vaccine. On June 17, The FDA authorized both the Pfizer and Moderna vaccines for use in children ages 6 months to four years. We believe children under 5 should be vaccinated as soon as possible. We would anticipate, with the start of school on August 5 and the low vaccination rates in our county, that we’ll have a marked increase in the number of infected patients. All Monterey County residents should get up to date on COVID-19 vaccinations as soon as possible. 

Monterey County Health Department
Monterey County Health Department

On 7/15/22, the United States had 94,037 documented new infections. There were also 207 deaths. Twenty-one states did not report their infections, and 28 states didn’t report their deaths. In the United States the number of hospitalized patients has been increasing in many areas and was 40,650 on July 15, an increase of 20% compared to the previous 14 days. Now there are 4,180 patients who are seriously or critically ill; that number was 3,400 two weeks ago. The number of critically ill patients has increased by 780 in the last 14 days, while at least 5,412 new deaths occurred (an increase of 29 deaths per day from the previous 14 days). The number of critically ill patients has increased for the sixth time in twenty-three 14-day periods. Patients are still dying each day (average 387/day). Omicron BA.2, BA.2.12.1, BA.4, and BA.5 variants causing infections should continue to increase and critically ill patients may continue to increase. Deaths, which usually lag two to four weeks behind exponential increase in infections, are increasing now. Past infections with a BA.1 or BA.2 variant will not prevent infections with BA.2.12.1, BA.4, or BA.5. 

As of 7/15/22, we have had 1,048,693 deaths and 91,170,571 SARS-CoV-2 infections in the United States. We have had 1,663,488 new infections in the last 14 days. We are adding an average of 831,744 infections every seven days. For the pandemic in the United States we are averaging one death for every 86.94 infections or over 11,503 deaths for each one million infections. As of 7/15/22, thirty-eight states have had greater than 500,000 total infections, and 37 states have had greater than 5,000 total deaths. Seventeen states (Virginia, Missouri, North Carolina, Indiana, Tennessee, Massachusetts, Ohio, Michigan, Georgia, Illinois, New Jersey, Pennsylvania, Florida, Texas, New York, Arizona and California) have had greater than 20,000 deaths. Four states (Florida, Texas, New York, and California) have had greater than 70,000 deaths. California and Texas have each had greater than 89,000 deaths with California having 93,017 deaths (20th most deaths in the world). 

As of 7/1/22, in the United States, 26.72% of the population has had a documented SARS-CoV-2 infection. In the last 18 months, 23.97% of our country became infected with SARS-CoV-2. On 11/20/20, there were 260,331 (cumulative) deaths in the US from SARS-CoV-2. In the last 18 months, there were 788,562 new deaths from SARS-CoV-2. For fifteen of those months, vaccines have been available to all adults. During these fifteen months, 477,596 people have died of SARS-CoV-2 infections. Most of the hospitalizations and deaths could have been prevented by vaccination, proper masking, and social distancing. 

As of 7/15/22, California was ranked 32th in the USA in infection percentage at 26.27%. In California, 22.3% of people were infected in the last 18 months. As of 7/15/22, 38 states have had greater than 25% of their population infected. 

Worldwide, average deaths per day are 1,846 for the last 14 days. The United States has 20.96% (387 per day) of all deaths per day in the world over the last two weeks. Worldwide infections per day were 910,374. The United States accounts for 13.05% of those infections (or 118,821 infections per day). 

Watching World Data

Over the next few months, we’ll be paying close attention to correlations between the SARS-CoV-2 data, the number of isolates identified in various countries and states, and the non-pharmaceutical interventions (like mask mandates and lockdowns) put in place by state and national governments. Data on infections, deaths, and percent of population infected was compiled from Worldometers. Data for this table for SARS-CoV-2 Isolates Currently Known in Location was compiled from GISAID and the CDC. It’s worth noting that GISAID provided more data than the CDC.

LocationTotal Infections as of 7/15/22New Infections on 7/15/22Total DeathsNew Deaths on 7/15/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World566,343,288(12,745,232 new infections in 14 days).903,2726,385,820(25,848 new deaths in last 14 days)1,7377.26%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617.2 (India)BV-1 (Texas, USA)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Theta/P.3 (Philippines) Mu/B.1.621 (Colombia)C.1.2 (South Africa 2% of isolates in July 2021)R1 (Japan)Omicron/B.1.1.529 + BA.1 + BA.2 + BA.3 (South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)Four new recombinants 12/31 to 3/22)BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)NoNo
USA91,170,571(ranked #1) 1,663,488 new infections in the last 14 days.
94,037(ranked #4)
21 states failed to report infections.
1,048,693(ranked #1) 5,412 new deaths in the last 14 days. 207
27 states failed to report deaths.
26.72%*
*Not updated
B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan)         Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)Recombinant Delta AY.119.2- Omicron BA.1.1 (Tennessee, USA 12/31/21)\BA.2BA.2.12.1 (United States)BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India)NoNo
Brazil33,250,117(ranked #3) 816,054 new infections in the last 14 days. 107,959 (ranked #4)675,145(ranked #2; 3,145 new deaths in 14 days)29915.42%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
India 43,730,071(ranked #2); 241,552 new infections in 2 weeks.20,044
525,660(ranked #3)563.10%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)APTK India VOI 32421Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Iota/B.1.526 (USA-NYC) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2.75 (India)NoNo
United Kingdom*
*No reported data for 7/14/22- 7/16/22
23,075,360(ranked #6) 334,295 new infections in 2 weeks.181,580 (ranked #7) 33.63%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)C.1.2 (South Africa)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)XD (AY.4/BA.1) recombinantXF (Delta/BA.1) recombinantXE (BA.1/BA.2) recombinantBA.2BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India)NoNo
California, USA10,380,889(ranked #12 in the world;  226,544 new infections in the last 14 days).8,69493,017 (ranked #20 in world)
397 new deaths in the last 14 days
1626.27%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa)BA.5 (South Africa)NoNo
Mexico6,373,876(ranked #18) 339,174 new infections in 14 days).34,885(ranked #9)326,335(ranked #5)744.84%B2 lineageAlpha/B.1.1.7 (UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
South Africa3,999,751(ranked #33; 5,528 new infections in 14 days).406101,918 (ranked #18)36.57%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)       C.1.2 (South Africa, July 2021)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)NoNo
Canada4,007,463(ranked #32) 61,376 new infections in 14 days).1,88143,555(ranked #24)5110.43% .B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
Poland6,029,947 (ranked #21; 14,313 new infections in 14 days). 1,974116,470 (ranked #15)215.96%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3 NoNo
Russia18,480,934(ranked #9), 47,540 new infections in 14 days).4,457381,794(ranked #4 in world)4012.65%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)R1 (Japan) B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Argentina9,426,171(ranked #14; 58,999 new infections in 14 days).———–140,365 (ranked #14)——–20.47%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gama/P.1 (Brazil)Delta/B.1.617.2 (India)Lambda/C.37 (Peru)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Colombia6,223,497(ranked #19, 48,316 new infections in 14 days).3,523140,365 (ranked #13)2611.97%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Epsilon/B.1.427 + B.1.429 (USA)*Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Peru3,714,361(ranked #38, 84,565 new infections in 14 days). 10,610235,526(ranked #6)1510.95%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Iran7,270,023(ranked 17th; 31,434 new infections in last 14 days)4,772141,477(ranked #11)138.43%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)


NoNo
Spain13,090,476(ranked 11th;   272,292 new infections in 14 days).19,211(ranked #12)109,348 (ranked #17)13427.97%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
France32,818,901 (ranked #4; 1,609,976 new infections in the last 14 days).119,684 (ranked #1)150,576 (ranked #10)10850.05%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinantNoNo
Germany29,692,989(ranked #5; 1,300,360 new infections in 14 days.).123,046 (ranked #2)142,535 (ranked #11)13435.21%
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
South Korea18,680,142 (ranked #9 310,285 new infections in 14 days).38,864(ranked #8)24,712 (ranked #38) 1636.37%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Vietnam10,759,145 (ranked #12; 11,748 new infections in 14 days).95643,090 (ranked #26)10.85%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Netherlands8,274,234 (ranked #16; 83,979 new infections in 14 days).6,52722,422 (ranked #41)548.07%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
Denmark3,039,859 (ranked #39) 23,810  new infections in 14 days1,5676,551 (ranked #81)852.10%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo




North Korea (DPRK)4,770,400 (ranked #24; 25,670 new infections in 14 days)5007418.34%Omicron/B.1.1.529 South Africa November 2021)NoNo
Taiwan4,215,200(ranked #30)
412,171 new infections in 14 days
25,310 (ranked #10)7,917 (ranked #73)11417.63%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Japan10,000,720(ranked #13)
671,200 new infections in the last 14 days
97,339(ranked #5)31,528(ranked #34)347.95%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo

What Our Team Is Reading This Week

COVID-19

SARS-CoV-2 Update

It’s time for our next 14-day moving average determinations for SARS-CoV-2 for the United States and my thoughts on vaccines, SARS-CoV-2 therapeutic agents and mutant viruses. We use the WORLDOMETERS aggregators data set to make any projections since it includes data from the Department of Veterans Affairs, the U.S. Military, federal prisons and the Navajo Nation.

SARS-CoV-2 infections per day have been increasing in the United States for 14 consecutive weeks despite underreporting by states and the failure to capture positive home tests and a decreased screening program in most states. Deaths per day had been decelerating at a rapid rate in the United States but are now increased by 8 more deaths per day. The number of infections have increased as the Omicron BA.2.12.1, BA.2, BA.4, and BA.5 variants of SARS CoV-2 have spread across the nation. The CDC estimates that BA.2.12.1 accounted for 42% of isolates, BA.2 accounted for 5.7%, BA.5 accounted for 36.6%, BA.4 accounted for 15.7%, and B.1.1.529 accounted for 0% in the week ending June 25.

CDC

We frequently hear messaging from health officials and politicians that Omicron is “mild,” especially compared to the Delta variant, and as a result, many of our patients believe that they no longer need to wear their masks. This is a dangerous misconception. SARS-CoV-2 still remains a highly transmissible, airborne virus. The following graph, based on CDC data from April 2, 2022, shows that Omicron deaths in people over 65 are much higher than Delta deaths in the same age group. In fact, the peak of Omicron deaths in people over 65 years of age is 163% higher than the Delta peak. The death rate from Omicron is only lower than Delta in the populations between 12 and 64 years of age. Until we have more data on these newer mutants of SARS-CoV-2, we will not know the lethality of each variant. It may take months to measure objective differences in the death rates of new circulating variants. We recommend that all of our patients and family members continue to wear N95 masks in all enclosed spaces.

In patients treated with Paxlovid for five days who have persistent symptoms and continued positivity, we feel that clinicians should consider giving a second course of Paxlovid for five days. Boucau et al have demonstrated that in a study of seven patients with recurrent symptoms, “High viral loads (median 6.1 log10 copies/mL) were detected after rebound for a median of 17 days after initial diagnosis. Three had culturable virus for up to 16 days after initial diagnosis.” This was not due to resistance-associated mutations of the virus, suggesting that the course of therapy may be inadequate in this group of persistently infected patients. 

NY Times

According to the UK Health Security Agency, “BA.4 shares all mutations/deletions with the BA.2 lineage except the following: S: 69/70 deletion, R408 (WT, wild type)*, L452R, F486V, Q493 (WT); ORF 7b: L11F; N: P151S; synonymous SNP G12160A” and “BA.5 shares all mutations/deletions with the BA.2 lineage except the following: S: 69/70 deletion, R408 (WT), L452R, F486V, Q493 (WT); ORF6: D61 (WT); M: D3N; synonymous SNPs: G12160A, A27038G, and C27889T.” On May 12, the European CDC designated both BA.4 and BA.5 as variants of concern. 

The Omicron variant has continued to mutate just like Delta. There are now 199 Omicron sub-variants (an increase of 42 in the last two weeks) that have been assigned Pango lineages, including 104 sub-lineages of BA.2 (an increase of 12 in two weeks), one sub-lineage of BA.3, nine sub-lineages of BA.4 (an increase of 6 in two weeks), and 15 sub-lineages of BA.5 (an increase of 10 in two weeks). The BF lineage (new two weeks ago), with BF.1 first detected in England, Denmark, Spain and Scotland now has 6 sublineages. The BE lineage (also new two weeks ago), with BE.1 first detected in South Africa, Austria and England, now has 3 new sublineages. There are also new lineages: BC.1 (Japan), BC.2 (Peru),BD.1 (UK), BG.1 (Peru), BG.2 (US, Denmark, Canada), BG.3 (Peru), BG.4 (Israel). 

An additional problem may be the development of recombinant SARS-CoV-2 isolates. A recombinant isolate occurs when two isolates infect the same cell and, in the process of viral reproduction, exchange nucleic acids, creating a new isolate that is a recombination of parts from the genomes of both isolates. A recombinant isolate of Delta AY.4.2.2 and Omicron BA.1.1 was recently reported in the UK. As of 3/25/22 four different recombinant variants of SARS-CoV-2 have been reported by the UK Health Security Agency. 

According to the UK Health Security Agency’s Technical Briefing from 3/25/22: “There are currently 3 recombinant lineages being monitored as part of horizon scanning: XD, XE, and XF (Figure 6). XD and XF are Delta and BA.1 recombinants. XE is a BA.1 and BA.2 recombinant and has 3 mutations that are not present in all BA.1 or BA.2 sequences: NSP3 C3241T and V1069I, and NSP12 C14599T. XF and XE are associated with UK sequenced samples. XD is predominantly associated with France. XD contains the unique mutation NSP2:E172D.” As of 5/17/22 the UK Health Security Agency reports 2,049 sequences of the XE recombinant in the UK data. 

Unless people continue to wear masks and get vaccinated, including their third dose of the vaccine, we will see further spread of the Omicron variants and increase in deaths in people who are not vaccinated, have waning immunity, the immunocompromised population and others with risk factors particularly those older over the age of 64. SARS-CoV-2 is now in the top ten most common causes of death for children. Anyone over the age of 5 years can now get vaccinated in the United States at no cost. This should get done immediately.In Monterey County, as of 7/3/22, only 0.6% of 0-4 year-olds and 43.2% of 5-11 year-olds have received the first two doses of vaccine, while 78.7% of 12-17 year-olds have received two doses. On June 17, The FDA authorized both the Pfizer and Moderna vaccines for use in children ages 6 months to four years. We believe children under 5 should be vaccinated as soon as possible. 

Monterey County Health Department

On 7/1/22, the United States had 102,788 documented new infections. There were also 283 deaths. Twenty-one states did not report their infections, and 27 states didn’t report their deaths. In the United States the number of hospitalized patients had been increasing in many areas. Now there are 3,400 patients who are seriously or critically ill; that number was 3,006 two weeks ago. The number of critically ill patients has increased by 394 in the last 14 days, while at least 5,106 new deaths occurred (an increase of 8 deaths per day from the previous 14 days). The number of critically ill patients has increased for the fifth time in twenty-two 14-day periods. Patients are still dying each day (average 358/day). Omicron BA.2, BA.2.12.1, BA.4, and BA.5 variants causing infections should continue to increase and critically ill patients may continue to increase. Deaths, which usually lag two to four weeks behind exponential increase in infections, are increasing now. Past infections with a BA.1 or BA.2 variant will not prevent infections with BA.2.12.1, BA.4, or BA.5. 

As of 7/1/22, we have had 1,043,281 deaths and 89,507,083 SARS-CoV-2 infections in the United States. We have had 1,538,264 new infections in the last 14 days. We are adding an average of 769,312 infections every seven days. For the pandemic in the United States we are averaging one death for every 86.2 infections or over 11,656 deaths for each one million infections. As of 7/1/22, thirty-eight states have had greater than 500,000 total infections, and 36 states have had greater than 5,000 total deaths. Seventeen states (Virginia, Missouri, North Carolina, Indiana, Tennessee, Massachusetts, Ohio, Michigan, Georgia, Illinois, New Jersey, Pennsylvania, Florida, Texas, New York, Arizona and California) have had greater than 20,000 deaths. Four states (Florida, Texas, New York, and California) have had greater than 70,000 deaths. California and Texas have each had greater than 89,000 deaths with California having 92,621 deaths (20th most deaths in the world). 

As of 7/1/22, in the United States, 26.72% of the population has had a documented SARS-CoV-2 infection. In the last 18 months, 23.97% of our country became infected with SARS-CoV-2. On 11/20/20, there were 260,331 (cumulative) deaths in the US from SARS-CoV-2. In the last 18 months, there were 783,150 new deaths from SARS-CoV-2. For fifteen of those months, vaccines have been available to all adults. During these fifteen months, 472,184 people have died of SARS-CoV-2 infections. Most of the hospitalizations and deaths could have been prevented by vaccination, proper masking, and social distancing. 

As of 7/1/22, California was ranked 35th in the USA in infection percentage at 25.69%. In California, 21.72% of people were infected in the last 18 months. As of 7/1/22, 36 states have had greater than 25% of their population infected. 

Worldwide, average deaths per day are 1,470 for the last 14 days. The United States has 24.35% (358 per day) of all deaths per day in the world over the last two weeks. Worldwide infections per day were 712,693. The United States accounts for 15.42% of those infections (or 109,902 infections per day). 

FDA-Approved Oral Drug Treatments for SARS-CoV-2

Pfizer has developed PAXLOVID™, an oral reversible inhibitor of C3-like protease of SARS-CoV-2. The drug inhibits this key enzyme that is crucial for virus production. The compound, also called Compound 6 (PF-07321332), is part of the drug combination PAXLOVID™ (PF-07321332; ritonavir), which just successfully completed a Phase 2-3 trial in humans in multiple countries. The preliminary results were announced on 11/5/21 by Pfizer. The results show that 89% of the hospitalizations and deaths were prevented in the drug treatment arm. The drug was administered twice a day for five days. No deaths occurred in the treatment group, and ten deaths occurred in the placebo group. The study was stopped by an independent data safety monitoring board, and the FDA concurred with this decision. Pfizer applied for an Emergency Use Authorization for this drug on 11/15/21. This drug was approved on 12/23/21. We have only been able to obtain PAXLOVID™ for two patients who we successfully treated with this drug obtained from CVS in Salinas (East Alisal Street; phone number 831-424-0026). They were expecting another shipment on 1/28/22. In my opinion, this agent, if more widely available, could markedly alter the course of every coronavirus infection throughout the world. 

Merck has developed the oral drug Molnupiravir, which induces RNA mutagenesis by viral RNA-dependent RNA polymerase of SARS-CoV-2 and other viruses. According to Kabinger et al, “Viral RNA-dependent RNA polymerase uses the active form of Molnupiravir, β-D-N4-hydroxycytidine triphosphate, as a substrate instead of cytidine triphosphate or uridine triphosphate. When the RNA-dependent RNA polymerase uses the resulting RNA as a template, β-D-N4-hydroxycytidine triphosphate directs incorporation of either guanine or adenine, leading to mutated (viral) RNA products. Analysis of RNA-dependent RNA polymerase–RNA complexes that contain mutagenesis products has demonstrated that β-D-N4-hydroxycytidine (the active form of Molnupiravir) can form stable base pairs with either guanine or adenine in RNA-dependent RNA polymerase explaining how the polymerase escapes proofreading and synthesizes mutated RNA” (quotation modified for clarity). The results of the phase 3 trial of Molnupiravir were published in the NEJM article “Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients” by Angélica Jayk Bernal, M.D. et al. (December 16, 2021 DOI: 10.1056/NEJMoa2116044). In this phase 3 study in the Molnupiravir group, 28 patients were hospitalized and one death occurred. In the placebo group, 53 patients were hospitalized and 9 died. Overall, 47% of hospitalizations and deaths were prevented by Molnupiravir. If you do a post hoc analysis and just look at deaths, Molnupiravir would prevent 89% of deaths. An Emergency Use Authorization by the FDA for Molnupiravir was approved on 12/24/21.The dose of Molnupiravir approved is four 200 mg capsules orally twice a day for five days. Diarrhea is reportedly a side effect in two percent of patients. I treated my first patient with Molnupiravir on 1/28/22. Currently more Molnupiravir is available weekly in the United States than PAXLOVID™ (see chart below; data from PHE.gov). Locally Molnupiravir is still available at CVS in Monterey (Fremont Blvd.; phone number: 831-375-5135) and CVS in Salinas (East Alisal Street; phone number 831-424-0026). 

FDA Approved Intramuscular Prophylaxis of SARS-CoV-2 Immunocompromised Patients

Evusheld (from AstraZeneca) contains two human monoclonal antibodies, Tixagevimab (150 mg in 1.5 mL) and Cilgavimab (150 mg in 1.5 mL), in separate vials. According to the manufacturer, “Tixagevimab and Cilgavimab are two recombinant human IgG1κ monoclonal antibodies with amino acid substitutions to extend antibody half-life (YTE), reduce antibody effector function, and minimize the potential risk of antibody-dependent enhancement of disease (TM). Tixagevimab and Cilgavimab can simultaneously bind to non-overlapping regions of the receptor binding domain (RBD) of SARS-CoV-2 spike protein. Tixagevimab, Cilgavimab, and their combination bind to spike protein with equilibrium dissociation constants of KD = 2.76 pM, 13.0 pM and 13.7 pM, respectively, blocking its interaction with human ACE2, the SARS-CoV-2 receptor, which is required for virus attachment. Tixagevimab, Cilgavimab, and their combination blocked RBD binding to human ACE2 with IC50 values of 0.32 nM (48 ng/mL), 0.53 nM (80 ng/mL), and 0.43 nM (65 ng/mL), respectively.” Each monoclonal antibody is administered intramuscularly to immunocompromised patients in two separate injections every six months. Evusheld availability in California is limited and has been rationed/distributed by our local Public Health Department only to hospitals. Physicians in Monterey County who want to receive a distribution (or redistribution) of Evusheld need to be added to the list of eligible facilities by the State Therapeutics group. The first step is for the Monterey County EMS Agency (phone: 831-755-5713) to make a request to the State Therapeutics group to have the facility added to the system for further verification.  Due to extremely limited availability, evidently the State Therapeutics group is currently only considering additions on a case by case basis.  Physicians who wish to submit their facility for consideration will need to provide the following information to the Monterey County EMS Agency:

  1. Facility/Provider Name for Registration
  2. Provider Type (Hospital, Pharmacy, Etc)
  3. Shipping Address
  4. Contact Name(s)
  5. Contact Email(s)
  6. Contact Phone Number(s)

As for my immunocompromised patients: We provided this information by email to the Monterey County EMS Agency on 1/26/22 and will update you when or if we become an eligible provider and receive our first doses of Evusheld. 

On 2/24/22, the FDA revised its dosing guidance for Evusheld, doubling the dosage of its two components, Tixagevimab and Cilgavimab, from 150 mg each to 300 mg each. They explain, “Based on the most recent information and data available, Evusheld may be less active against certain Omicron subvariants. The dosing regimen was revised because available data indicate that a higher dose of Evusheld may be more likely to prevent infection by the COVID-19 Omicron subvariants BA.1 and BA.1.1 than the originally authorized Evusheld dose.” Patients who have already received their first administration of Evusheld intramuscularly will need to contact their healthcare provider to get a second 150 mg injection of Tixagevimab and Cilgavimab. If you have not received Evusheld yet, the correct dose is 3 mL/300 mg of each monoclonal antibody injected intramuscularly. This large volume necessitates administration of the antibodies in the gluteus, with two separate injections. 

Watching World Data

Over the next few months, we’ll be paying close attention to correlations between the SARS-CoV-2 data, the number of isolates identified in various countries and states, and the non-pharmaceutical interventions (like mask mandates and lockdowns) put in place by state and national governments. Data on infections, deaths, and percent of population infected was compiled from Worldometers. Data for this table for SARS-CoV-2 Isolates Currently Known in Location was compiled from GISAID and the CDC. It’s worth noting that GISAID provided more data than the CDC.

LocationTotal Infections as of 7/1/22New Infections on 7/1/22Total DeathsNew Deaths on 7/1/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World553,598,056(9,977,707 new infections in 14 days).825,0086,359,972(20,585 new deaths in last 14 days)1,5037.10%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617.2 (India)BV-1 (Texas, USA)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Theta/P.3 (Philippines) Mu/B.1.621 (Colombia)C.1.2 (South Africa 2% of isolates in July 2021)R1 (Japan)Omicron/B.1.1.529 + BA.1 + BA.2 + BA.3 (South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)Four new recombinants 12/31 to 3/22)BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)NoNo
USA89,507,083(ranked #1) 1,538,264 new infections in the last 14 days.
102,788(ranked #2)
21 states failed to report infections.
1,043,281(ranked #1) 5,016 new deaths in the last 14 days. 283
27 states failed to report deaths.
26.72%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan)         Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)Recombinant Delta AY.119.2- Omicron BA.1.1 (Tennessee, USA 12/31/21)\BA.2BA.2.12.1 (United States)BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India)NoNo
Brazil32,434,063(ranked #3) 760,688 new infections in the last 14 days. 75,612 (ranked #5)671,700(ranked #2; 2,732 new deaths in 14 days)23415.04%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
India 43,488,519(ranked #2); 204,726 new infections in 2 weeks.17,237525,168(ranked #3)293.09%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)APTK India VOI 32421Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Iota/B.1.526 (USA-NYC) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2.75 (India)NoNo
United Kingdom22,741,065(ranked #6) 268,562 new infections in 2 weeks.20,720180,417 (ranked #7) 880 new deaths in 2 weeks8733.15%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)C.1.2 (South Africa)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)XD (AY.4/BA.1) recombinantXF (Delta/BA.1) recombinantXE (BA.1/BA.2) recombinantBA.2BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)BA.2.75 (India)NoNo
California, USA10,154,345(ranked #12 in the world;  262,248 new infections in the last 14 days).23,52492,620 (ranked #20 in world)
439 new deaths in the last 14 days
6025.69%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1 (United States)BA.4 (South Africa)BA.5 (South Africa)NoNo
Mexico6,034,602(ranked #20) 182,006 new infections in 14 days).24,537(ranked #9)325,716(ranked #5)474.58%B2 lineageAlpha/B.1.1.7 (UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
South Africa3,994,223(ranked #31; 9,577 new infections in 14 days).380101,804 (ranked #18)166.56%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)       C.1.2 (South Africa, July 2021)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)NoNo
Canada3,946,087(ranked #32) 35,876 new infections in 14 days).42,010(ranked #25)10.27% .B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
Poland6,015,634 (ranked #21; 4,715 new infections in 14 days). 643116,429 (ranked #15)515.92%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3 NoNo
Turkey15,123,331(ranked #10, 37,582 new infections in 14 days).————99,032 (ranked #19)———17.51% B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
Russia18,433,394(ranked #8), 41,597 new infections in 14 days).3,155381,165(ranked #4 in world)5312.62%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)R1 (Japan) B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Argentina9,367,172(ranked #14; 53,619 new infections in 14 days).———–129,070 (ranked #14)——–20.35%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gama/P.1 (Brazil)Delta/B.1.617.2 (India)Lambda/C.37 (Peru)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Colombia6,175,181(ranked #18, 43,424 new infections in 14 days).140,070 (ranked #14)11.88%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Epsilon/B.1.427 + B.1.429 (USA)*Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Peru3,629,796(ranked #38, 33,432 new infections in 14 days). 4,706235,526(ranked #6)2910.71%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Iran7,238,589(ranked 17th; 4,066 new infections in last 14 days)463141,390(ranked #11)18.40%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)


NoNo
Spain12,818,184(ranked 11th;   254,785 new infections in 14 days).28,048(ranked #8)108,111 (ranked #17)8927.39%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
France31,208,925 (ranked #4; 1,129,467 new infections in the last 14 days).125,066 (ranked #1)149,585 (ranked #10)5247.60%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinantNoNo
Germany28,392,629(ranked #5; 1,268,170 new infections in 14 days.).98,669 (ranked #3)141,292 (ranked #12)10333.67%
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
South Korea18,368,857 (ranked #9 105,214 new infections in 14 days).9,516(ranked #17)24,555 (ranked #39) 835.76%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Vietnam10,747,397 (ranked #12; 10,989 new infections in 14 days).92743,087 (ranked #24)10.84%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Netherlands8,190,255 (ranked #15; 67,997 new infections in 14 days).6,08322,380 (ranked #41)247.58%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
Denmark3,016,049 (ranked #39) 19,336  new infections in 14 days1,4556,471 (ranked #81)251.70%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo




North Korea (DPRK)4,744,430 (ranked #24; 163,010 new infections in 14 days)4,570 7318.24%Omicron/B.1.1.529 South Africa November 2021)NoNo
Taiwan3,803,029(ranked #38)
612,283 new infections in 14 days
35,780 (ranked #6)6,772 (ranked #79)121 15.91%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Japan9,329,520(ranked #14)
221,197 new infections in the last 14 days
23,523(ranked #10)31,281(ranked #31)157.42%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo

What Our Team Is Reading This Week

COVID-19

SARS-CoV-2 Update

It’s time for our next 14-day moving average determinations for SARS-CoV-2 for the United States and my thoughts on vaccines, SARS-CoV-2 therapeutic agents and mutant viruses. We use the WORLDOMETERS aggregators data set to make any projections since it includes data from the Department of Veterans Affairs, the U.S. Military, federal prisons and the Navajo Nation.

SARS-CoV-2 infections per day have been increasing in the United States for 6 consecutive weeks despite underreporting by states and the failure to capture positive home tests and a decreased screening program in most states. The number of infections per day in the United States has increased by 49.28% in the last 2 weeks and 136.4% from 4 weeks ago. Deaths per day had been decelerating at a rapid rate in the United States but are now flattening out. The rate of decline has lessened as the increased infection rate and infectivity of the Omicron BA.1, BA.2 and particularly BA.2.12.1 variant of SARS CoV-2 have spread across the nation. The CDC estimates that BA.2.12.1 accounted for 57.9% of isolates in the week ending May 21.

Something to look out for is the rise of infections in South Africa to 94,255 infections in the last 14 days ending 5/20/22, a 31% increase from the previous two weeks. This is secondary to new Omicron mutants BA.4 and BA.5, which, according to NICD, became the dominant variants in South Africa in April, comprising 58% of isolates and now make up 92% of isolates. According to the UK Health Security Agency, “BA.4 shares all mutations/deletions with the BA.2 lineage except the following: S: 69/70 deletion, R408 (WT, wild type)*, L452R, F486V, Q493 (WT); ORF 7b: L11F; N: P151S; synonymous SNP G12160A” and “BA.5 shares all mutations/deletions with the BA.2 lineage except the following: S: 69/70 deletion, R408 (WT), L452R, F486V, Q493 (WT); ORF6: D61 (WT); M: D3N; synonymous SNPs: G12160A, A27038G, and C27889T.” As of 5/20/22, 0.77% of cases sequenced in the United States are BA.4 and 0.78% are BA.5. On May 12, the European CDC designated both BA.4 and BA.5 as variants of concern. 

European Centre for Disease Prevention and Control

The Omicron variant will continue to mutate just like Delta. There are now 100 Omicron sub-variants that have been assigned Pango lineages, including 50 sub-lineages of BA.2.

An additional problem may be the development of recombinant SARS-CoV-2 isolates. A recombinant isolate occurs when two isolates infect the same cell and, in the process of viral reproduction, exchange nucleic acids, creating a new isolate that is a recombination of parts from the genomes of both isolates. A recombinant isolate of Delta AY.4.2.2 and Omicron BA.1.1 was recently reported in the UK. As of 3/25/22 four different recombinant variants of SARS-CoV-2 have been reported by the UK Health Security Agency. 

According to the UK Health Security Agency’s Technical Briefing from 3/25/22: “There are currently 3 recombinant lineages being monitored as part of horizon scanning: XD, XE, and XF (Figure 6). XD and XF are Delta and BA.1 recombinants. XE is a BA.1 and BA.2 recombinant and has 3 mutations that are not present in all BA.1 or BA.2 sequences: NSP3 C3241T and V1069I, and NSP12 C14599T. XF and XE are associated with UK sequenced samples. XD is predominantly associated with France. XD contains the unique mutation NSP2:E172D.” As of 5/17/22 the UK Health Security Agency reports 2,049 sequences of the XE recombinant in the UK data. 

Omicron variants have mutations which decrease the effectiveness of current vaccines and monoclonal antibodies. The effectiveness of the new Pfizer drug, PAXLOVIDTM, should not be compromised by any of the current mutations in Omicron or Delta variants. Pfizer completed their filing with the FDA on 11/15/21. The FDA approved PAXLOVIDTM on December 22 , 2021.The FDA approved Merck’s drug Molnupiravir on December 23, 2021. On 12/23/21 CVS announced by fax it was selected by the Government to distribute oral PAXLOVIDTM and Molnupiravir. On 12/27/21, another fax from CVS listed which CVS pharmacies in California would have these drugs. Monterey County covers 3,771 square miles with a population of 434,061. Three CVS pharmacies in Monterey, Salinas, and Soledad are the only listed pharmacies in our county. I have now been able to obtain PAXLOVIDTM for infected patients from the CVS in Salinas (phone 831-424-0026), the CVS on Fremont Street in Monterey (phone 831-375-5135) and the CVS in Soledad in south Monterey County (phone 831-678-5110). All require electronic prescriptions written as Paxlovid three tablets twice daily orally for five days (thirty total tablets).  Physicians or their staff probably should call to check on drug availability that day.

In the absence of obtaining intravenous Sotrovimab or Bebtelovimab, only oral PAXLOVIDTM and Molnupiravir are available to treat SARS-CoV-2 as an outpatient. Our first Paxlovid failure in an immunocompromised patient was treated the week of 4/5/22 at the Community Hospital of the Monterey Peninsula (Montage) ER as an outpatient with a single one-minute intravenous injection of Bebtelovimab. 

Vaccination will not prevent you from getting an Omicron variant infection. For now only masking (N95 rated masks, please!) and social distancing will have any effect on acquisition of infection with these variants. Furthermore, we do not believe that a 5-day quarantine or isolation period is sufficient for any COVID-19 infection.

In the last 14 days in the United States, the number of infections has increased by 32,374 infections per day compared to the preceding 14-day period. Our infections per day have increased for the third time in the last 14 weeks. Unless people get vaccinated, including their third dose of the vaccine, we will see further spread of the Omicron variants and increase in deaths in people who are not vaccinated, have waning immunity, the immunocompromised population and others with risk factors particularly those older over the age of 64. SARS-CoV-2 is now in the top ten most common causes of death for children. Anyone over the age of 5 years can now get vaccinated in the United States at no cost. This should get done immediately.In Monterey County, as of 5/24/22, only 38.3% of 5-11 year-olds have received the first two doses of vaccine, while 80.3% of 12-17 year-olds have received two doses.

Monterey County Health Department

On 5/20/22, the United States had 98,665 documented new infections. There were also 244 deaths. In the United States the number of hospitalized patients had been increasing in many areas. Now there are 2,289  patients who are seriously or critically ill; that number was 1,724 two weeks ago. The number of critically ill patients has increased by 565 in the last 14 days, while at least 4,355 new deaths occurred (a decrease of 33 deaths per day from the previous 14 days). The number of critically ill patients has increased for the second time in nineteen 14-day periods. Patients are still dying each day (average 311/day). Omicron BA.2  variants causing infections should continue to increase and critically ill patients may continue to increase. Deaths usually lag two to four weeks behind exponential increase in infections so we will have to see how lethal BA.2.12.1 infections are in a month. Infections with a BA.1, and BA.2 will not prevent infections with BA.2.12.1. There have already been reports out of Israel of patients infected with BA.1 being later reinfected with BA.2. 

As of 5/20/22, we have had 1,028,741 deaths and 84,935,202 SARS-CoV-2 infections in the United States. We have had 1,401,202 new infections in the last 14 days. We were adding an average of 700,601 infections every seven days. For the pandemic in the United States we are averaging one death for every 82.56 infections reported for each death or over 12,112 deaths for each one million infections. As of 5/20/22, thirty-seven states have had greater than 500,000 total infections, and 36 states have had greater than 5,000 total deaths. Seventeen states (Virginia, Missouri, North Carolina, Indiana, Tennessee, Massachusetts, Ohio, Michigan, Georgia, Illinois, New Jersey, Pennsylvania, Florida, Texas, New York, Arizona and California) have had greater than 20,000 deaths. Four states (Florida, Texas, New York, and California) have had greater than 69,000 deaths. California and Texas have each had greater than 88,000 deaths with California having 91,322 deaths (20th most deaths in the world). 

On 11/20/20 in the United States, 3.70% of the population had a documented SARS-CoV-2 infection. California was ranked 41st in infection percentage at 2.77%. On 11/20/21 in North Dakota, 9.18% of the population was infected (ranked #1), and in South Dakota, 8.03% of the population was infected (ranked #2). As of 5/20/22, in the United States, 25.38% of the population has had a documented SARS-CoV-2 infection. In the last 17 months, 22.73% of our country became infected with SARS-CoV-2. On 11/20/20, there were 260,331 (cumulative) deaths in the US from SARS-CoV-2. In the last 17 months, there were 768,610 new deaths from SARS-CoV-2. For fourteen of those months, vaccines have been available to all adults. During these fourteen months, 457,644 people have died of SARS-CoV-2 infections. Most of the hospitalizations and deaths could have been prevented by vaccination, proper masking, and social distancing. 

As of 5/20/22, California was ranked 37th in the USA in infection percentage at 23.90%. In California 20.06% of Californians were infected in the last 17 months. As of 5/20/22 forty-six states have had greater than 20% of their population infected. Rhode Island was at 36.53% (ranked #1), Alaska was at 34.10% (ranked #2), North Dakota was at 31.91% (ranked #3), Kentucky was at 30.09% (ranked #4), Tennessee was at 29.98% (ranked #5), Utah was at 29.42% (ranked #6), South Carolina was at 28.89% (ranked #7), Wisconsin jumped to 28.42% (ranked #8),West Virginia was at 28.41% (ranked #9), Florida jumped to 28.41% (ranked #10), Arizona was at 28.00% (ranked #12), Arkansas was at 28.73% (ranked #14) and Texas was at 23.75% (ranked #37) of their population infected.

The table below shows that if we rank the US states with the highest death rates per million population within the world rankings, we see that Mississippi, Arizona and Alabama have the eighth highest death rates, New Jersey, and Arkansas have the ninth highest COVID-19 deaths per million in the world. Louisiana had the tenth, New York was at eleventh, and Florida and Rhode Island were tied at twelth. The United States as a whole ranks 16th in the world for deaths per million population (3,108 deaths per million). California ranks 39th in the USA (and 36th in the world). If we look at the death rates per million in South Korea (465), Iceland (443), Japan (240), and Israel (1,161), they suggest that treatment outcomes are somehow different in these four countries. The same phenomenon can be seen in Scandinavia, where the death rate in Sweden is 1,851 per million, compared to 556 per million in Norway and 793 per million in Finland. The United States should have taken a closer look at how countries with low death rates (like South Korea, Iceland, Japan, Finland, and Norway) were preventing COVID-19 infections and treating COVID-19 patients. 

State or Country COVID-19 Deaths per million populationRank in USARanked within World
Mississippi4,1881st8th tied
New Jersey  3,7837th9th tied
Louisiana3,7248th10th 
New York 3,56013th11th 
Alabama4,0073rd8th tied
Arizona4,1572nd8th tied
Rhode Island  3,362 20th12th
Arkansas3,7886th9th tied
Florida3,46119th12th 
California2,31139th36th
USA3,10816th
Peru6,2981st
Bosnia-Herzegovina  4,8683rd
Hungary4,8314th
Montenegro4,3286th
Bulgaria5,4142nd
Czechia3,7479th
Brazil3,09016th
Georgia4,2297th
Sweden1,85156th
Israel1,16185th
Canada1,06092nd
Finland793109th
Norway556126th
Japan240149th
Iceland443132nd
South Korea465130th

FDA-Approved Oral Drug Treatments for SARS-CoV-2

Pfizer has developed PAXLOVID™, an oral reversible inhibitor of C3-like protease of SARS-CoV-2. The drug inhibits this key enzyme that is crucial for virus production. The compound, also called Compound 6 (PF-07321332), is part of the drug combination PAXLOVID™ (PF-07321332; ritonavir), which just successfully completed a Phase 2-3 trial in humans in multiple countries. The preliminary results were announced on 11/5/21 by Pfizer. The results show that 89% of the hospitalizations and deaths were prevented in the drug treatment arm. The drug was administered twice a day for five days. No deaths occurred in the treatment group, and ten deaths occurred in the placebo group. The study was stopped by an independent data safety monitoring board, and the FDA concurred with this decision. Pfizer applied for an Emergency Use Authorization for this drug on 11/15/21. This drug was approved on 12/23/21. We have only been able to obtain PAXLOVID™ for two patients who we successfully treated with this drug obtained from CVS in Salinas (East Alisal Street; phone number 831-424-0026). They were expecting another shipment on 1/28/22. In my opinion, this agent, if more widely available, could markedly alter the course of every coronavirus infection throughout the world. 

Merck has developed the oral drug Molnupiravir, which induces RNA mutagenesis by viral RNA-dependent RNA polymerase of SARS-CoV-2 and other viruses. According to Kabinger et al, “Viral RNA-dependent RNA polymerase uses the active form of Molnupiravir, β-D-N4-hydroxycytidine triphosphate, as a substrate instead of cytidine triphosphate or uridine triphosphate. When the RNA-dependent RNA polymerase uses the resulting RNA as a template, β-D-N4-hydroxycytidine triphosphate directs incorporation of either guanine or adenine, leading to mutated (viral) RNA products. Analysis of RNA-dependent RNA polymerase–RNA complexes that contain mutagenesis products has demonstrated that β-D-N4-hydroxycytidine (the active form of Molnupiravir) can form stable base pairs with either guanine or adenine in RNA-dependent RNA polymerase explaining how the polymerase escapes proofreading and synthesizes mutated RNA” (quotation modified for clarity). The results of the phase 3 trial of Molnupiravir were published in the NEJM article “Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients” by Angélica Jayk Bernal, M.D. et al. (December 16, 2021 DOI: 10.1056/NEJMoa2116044). In this phase 3 study in the Molnupiravir group, 28 patients were hospitalized and one death occurred. In the placebo group, 53 patients were hospitalized and 9 died. Overall, 47% of hospitalizations and deaths were prevented by Molnupiravir. If you do a post hoc analysis and just look at deaths, Molnupiravir would prevent 89% of deaths. An Emergency Use Authorization by the FDA for Molnupiravir was approved on 12/24/21.The dose of Molnupiravir approved is four 200 mg capsules orally twice a day for five days. Diarrhea is reportedly a side effect in two percent of patients. I treated my first patient with Molnupiravir on 1/28/22. Currently more Molnupiravir is available weekly in the United States than PAXLOVID™ (see chart below; data from PHE.gov). Locally Molnupiravir is still available at CVS in Monterey (Fremont Blvd.; phone number: 831-375-5135) and CVS in Salinas (East Alisal Street; phone number 831-424-0026). 

FDA Approved Intramuscular Prophylaxis of SARS-CoV-2 Immunocompromised Patients

Evusheld (from AstraZeneca) contains two human monoclonal antibodies, Tixagevimab (150 mg in 1.5 mL) and Cilgavimab (150 mg in 1.5 mL), in separate vials. According to the manufacturer, “Tixagevimab and Cilgavimab are two recombinant human IgG1κ monoclonal antibodies with amino acid substitutions to extend antibody half-life (YTE), reduce antibody effector function, and minimize the potential risk of antibody-dependent enhancement of disease (TM). Tixagevimab and Cilgavimab can simultaneously bind to non-overlapping regions of the receptor binding domain (RBD) of SARS-CoV-2 spike protein. Tixagevimab, Cilgavimab, and their combination bind to spike protein with equilibrium dissociation constants of KD = 2.76 pM, 13.0 pM and 13.7 pM, respectively, blocking its interaction with human ACE2, the SARS-CoV-2 receptor, which is required for virus attachment. Tixagevimab, Cilgavimab, and their combination blocked RBD binding to human ACE2 with IC50 values of 0.32 nM (48 ng/mL), 0.53 nM (80 ng/mL), and 0.43 nM (65 ng/mL), respectively.” Each monoclonal antibody is administered intramuscularly to immunocompromised patients in two separate injections every six months. Evusheld availability in California is limited and has been rationed/distributed by our local Public Health Department only to hospitals. Physicians in Monterey County who want to receive a distribution (or redistribution) of Evusheld need to be added to the list of eligible facilities by the State Therapeutics group. The first step is for the Monterey County EMS Agency (phone: 831-755-5713) to make a request to the State Therapeutics group to have the facility added to the system for further verification.  Due to extremely limited availability, evidently the State Therapeutics group is currently only considering additions on a case by case basis.  Physicians who wish to submit their facility for consideration will need to provide the following information to the Monterey County EMS Agency:

  1. Facility/Provider Name for Registration
  2. Provider Type (Hospital, Pharmacy, Etc)
  3. Shipping Address
  4. Contact Name(s)
  5. Contact Email(s)
  6. Contact Phone Number(s)

As for my immunocompromised patients: We provided this information by email to the Monterey County EMS Agency on 1/26/22 and will update you when or if we become an eligible provider and receive our first doses of Evusheld. 

On 2/24/22, the FDA revised its dosing guidance for Evusheld, doubling the dosage of its two components, Tixagevimab and Cilgavimab, from 150 mg each to 300 mg each. They explain, “Based on the most recent information and data available, Evusheld may be less active against certain Omicron subvariants. The dosing regimen was revised because available data indicate that a higher dose of Evusheld may be more likely to prevent infection by the COVID-19 Omicron subvariants BA.1 and BA.1.1 than the originally authorized Evusheld dose.” Patients who have already received their first administration of Evusheld intramuscularly will need to contact their healthcare provider to get a second 150 mg injection of Tixagevimab and Cilgavimab. If you have not received Evusheld yet, the correct dose is 3 mL/300 mg of each monoclonal antibody injected intramuscularly. This large volume necessitates administration of the antibodies in the gluteus, with two separate injections. 

Watching World Data

Over the next few months, we’ll be paying close attention to correlations between the SARS-CoV-2 data, the number of isolates identified in various countries and states, and the non-pharmaceutical interventions (like mask mandates and lockdowns) put in place by state and national governments. Data on infections, deaths, and percent of population infected was compiled from Worldometers. Data for this table for SARS-CoV-2 Isolates Currently Known in Location was compiled from GISAID and the CDC. It’s worth noting that GISAID provided more data than the CDC.

LocationTotal Infections as of 5/20/22New Infections on 5/20/22Total DeathsNew Deaths on 5/20/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World526,381,589(9,885,575 new infections in 14 days).760,7546,298,738(24,190  new deaths in last 14 days)1,3956.75%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617.2 (India)BV-1 (Texas, USA)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Theta/P.3 (Philippines) Mu/B.1.621 (Colombia)C.1.2 (South Africa 2% of isolates in July 2021)R1 (Japan)Omicron/B.1.1.529 + BA.1 + BA.2 + BA.3 (South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)Four new recombinants 12/31 to 3/22)BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)NoNo
USA84,935,262(ranked #1) 1,401,202 new infections in the last 14 days.98,665(ranked #2)1,028,741(ranked #1)4,355 new deaths in the last 14 days. 24425.38%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan)         Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)Recombinant Delta AY.119.2- Omicron BA.1.1 (Tennessee, USA 12/31/21)\BA.2BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)NoNo
Brazil30,762,413(ranked #3) 218,405 new infections in the last 14 days. 10,187 (ranked #11)665,595(ranked #2)10414.28%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
India43,134,332(ranked #2); 106,300 new infections in 2 weeks.2,510524,348(ranked #3)253.06%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)APTK India VOI 32421Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Iota/B.1.526 (USA-NYC) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
United Kingdom22,238,706(ranked #6; was #6 thirty-four weeks ago; 124,672 new infections in 2 weeks.6,338(ranked 16th in the world).177,977 ranked #7 in world)8732.43%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)C.1.2 (South Africa)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)XD (AY.4/BA.1) recombinantXF (Delta/BA.1) recombinantXE (BA.1/BA.2) recombinantBA.2BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)NoNo
California, USA9,446,122(ranked #13 in the world;  157,349 new infections in the last 14 days).16,04491,322 (ranked #20 in world)4723.90%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)BA.2BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)NoNo
Mexico5,752,441(ranked #20) 12,361 new infections in 14 days).———324,617(ranked #5)——–4.37%B2 lineageAlpha/B.1.1.7 (UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
South Africa3,921,633(ranked #29; 94,255 new infections in 14 days).6,375100,916 (ranked #18)186.45%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)       C.1.2 (South Africa, July 2021)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)BA.2BA.2.12.1BA.4 (South Africa)BA.5 (South Africa)NoNo
Canada3,787,378(ranked #31, was 26th eighteen weeks ago; 57,347 new infections in 14 days).2,29240,664(ranked #25)3710.02% .B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
Poland6,005,101 (ranked #20; 5,558 new infections in 14 days). 315116,255 (ranked #15)1315.89%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3 NoNo
Turkey15,060,112(ranked #10, 19,874 new infections in 14 days).————98,918 (ranked #19)———17.50% B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
Russia18,283,706(ranked #7), 51,635 new infections in 14 days).5,089378,168(ranked #4 in world)9612.51%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)R1 (Japan) B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Argentina9,135,308(ranked #13; 51,635 new infections in 14 days).———–128,776 (ranked #14 in world)——–19.87%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gama/P.1 (Brazil)Delta/B.1.617.2 (India)Lambda/C.37 (Peru)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Colombia6,099,111(ranked #18, 5,466 new infections in 14 days).———–139,833 (ranked #12 in the world)———11.75%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Epsilon/B.1.427 + B.1.429 (USA)*Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Peru3,574,876(ranked #35, 8,850 new infections in 14 days). 694213,086(ranked #6)910.56%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Indonesia6,097,986(ranked #18; —– new infections in 14 days)250156,513 (ranked #9)32.16%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Eta/B.1.525 (Nigeria/UK)Theta/P.3 (Philippines) Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)
NoNo
Iran7,229,582 5,151 new infections in last 14 days(ranked 16th; was 12th  thirty-four weeks ago)228141,262 (ranked #11)98.40%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)


NoNo
Spain12,238,073(ranked 11th;   229,014  new infections in 14 days).19,631105,947 (ranked #17)10126.15%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
France29,315,478 (ranked #4; 425,339 new infections in the last 14 days).24,332 (ranked #9)147,780 (ranked #10)6544.72%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinantNoNo
Germany26,053,934(ranked #5; 764,344 new infections in 14 days.).40,651 (ranked #5)138,633 (ranked #13)14530.91%
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
Hungary1,914,697 (ranked #44; 11,497 new infections in 14 days).
———46,446 (ranked #23)——–19.91%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Romania2,905,539(ranked #38; 7,281 new infections in 14 days).48465,644 (ranked#20)415.29%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
South Korea17,914,957 (ranked 8th) ; 450,175 new infections in 14 days).25,108(ranked#8)23,885 (ranked #39); 4334.88%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Ukraine5,009,301(ranked #22; 6,431new infections in 14 days),——–108,497 (ranked #16)——–11.58%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Vietnam10,706,111(ranked #12; 35,541new infections in 14 days).1,58743,075 (ranked #24)210.81%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Netherlands8,075,194 (ranked #15; 17,494 new infections in 14 days).1,04822,306 (ranked #41)546.93%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
Denmark2,979,238 (ranked #37) 8,429  new infections in 14 days———6,312 (ranked #81)———51.09%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo




North Korea (DPRK)First listing)2,241,618 (ranked#41)263,380 (ranked#1)8528.62%

What Our Team Is Reading This Week

COVID-19

SARS-CoV-2 Update

It’s time for our next 14-day moving average determinations for SARS-CoV-2 for the United States and my thoughts on vaccines, SARS-CoV-2 therapeutic agents and mutant viruses. We use the WORLDOMETERS aggregators data set to make any projections since it includes data from the Department of Veterans Affairs, the U.S. Military, federal prisons and the Navajo Nation.

SARS-CoV-2 infections per day have been increasing in the United States for 4 consecutive weeks despite underreporting by states and the failure to capture positive home tests and a decreased screening program in most states. The number of infections per day in the United States has increased by 59.7% in the last 2 weeks and 118.5% from 4 weeks ago. Deaths per day had been decelerating at a rapid rate in the United States but are now flattening out. The rate of decline has lessened as the increased infection rate and infectivity of the Omicron BA.1, BA.2 and particularly BA.2.12.1 variant of SARS CoV-2 have spread across the nation. The CDC estimates that BA.2.12.1 accounted for 36.5% of isolates in the week ending April 30.

Something to look out for is the rise of infections in South Africa from 25,393 infections in the 2 weeks ending on 4/22/22 to 71,869 infections in the last 14 days ending 5/6/22, a 283% increase. This is probably secondary to new Omicron mutants BA.4 and BA.5, which, according to NICD, became the dominant variants in South Africa in April, comprising 58% of isolates. According to the UK Health Security Agency, “BA.4 shares all mutations/deletions with the BA.2 lineage except the following: S: 69/70 deletion, R408 (WT, wild type)*, L452R, F486V, Q493 (WT); ORF 7b: L11F; N: P151S; synonymous SNP G12160A” and “BA.5 shares all mutations/deletions with the BA.2 lineage except the following: S: 69/70 deletion, R408 (WT), L452R, F486V, Q493 (WT); ORF6: D61 (WT); M: D3N; synonymous SNPs: G12160A, A27038G, and C27889T.” As of 5/8/22, the United States has sequenced 20 cases of BA.4 and 6 cases of BA.5. 

The Omicron variant will continue to mutate just like Delta. There are now 92 Omicron sub-variants that have been assigned Pango lineages, including 43 sub-lineages of BA.2.

An additional problem may be the development of recombinant SARS-CoV-2 isolates. A recombinant isolate occurs when two isolates infect the same cell and, in the process of viral reproduction, exchange nucleic acids, creating a new isolate that is a recombination of parts from the genomes of both isolates. A recombinant isolate of Delta AY.4.2.2 and Omicron BA.1.1 was recently reported in the UK. As of 3/25/22 four different recombinant variants of SARS-CoV-2 have been reported by the UK Health Security Agency. 

According to the UK Health Security Agency’s Technical Briefing from 3/25/22: “There are currently 3 recombinant lineages being monitored as part of horizon scanning: XD, XE, and XF (Figure 6). XD and XF are Delta and BA.1 recombinants. XE is a BA.1 and BA.2 recombinant and has 3 mutations that are not present in all BA.1 or BA.2 sequences: NSP3 C3241T and V1069I, and NSP12 C14599T. XF and XE are associated with UK sequenced samples. XD is predominantly associated with France. XD contains the unique mutation NSP2:E172D.”

As of 5/8/22 the UK Health Security Agency reports 1,880 sequences of the XE recombinant in the UK data. The figure below shows a breakdown of XE data by gender and age group. We can see there were more XE infections in children and young adults than there were in the 70+ age groups. 

Omicron variants have mutations which decrease the effectiveness of current vaccines and monoclonal antibodies. The effectiveness of the new Pfizer drug, PAXLOVIDTM, should not be compromised by any of the current mutations in Omicron or Delta variants. Pfizer completed their filing with the FDA on 11/15/21. The FDA approved PAXLOVIDTM on December 22 , 2021.The FDA approved Merck’s drug Molnupiravir on December 23, 2021. On 12/23/21 CVS announced by fax it was selected by the Government to distribute oral PAXLOVIDTM and Molnupiravir. On 12/27/21, another fax from CVS listed which CVS pharmacies in California would have these drugs. Monterey County covers 3,771 square miles with a population of 434,061. Three CVS pharmacies in Monterey, Salinas, and Soledad are the only listed pharmacies in our county. I have now been able to obtain PAXLOVIDTM for infected patients from the CVS in Salinas (phone 831-424-0026), the CVS on Fremont Street in Monterey (phone 831-375-5135) and the CVS in Soledad in south Monterey County (phone 831-678-5110). All require electronic prescriptions written as Paxlovid three tablets twice daily orally for five days (thirty total tablets).  Physicians or their staff probably should call to check on drug availability that day.

In the absence of obtaining intravenous Sotrovimab or Bebtelovimab, only oral PAXLOVIDTM and Molnupiravir are available to treat SARS-CoV-2 as an outpatient. Our first Paxlovid failure in an immunocompromised patient was treated the week of 4/5/22 at the Community Hospital of the Monterey Peninsula (Montage) ER as an outpatient with a single one-minute intravenous injection of Bebtelovimab. Vaccination will not prevent you from getting an Omicron variant infection. For now only masking (N95 rated masks, please!) and social distancing will have any effect on acquisition of infection with these variants. Furthermore, we do not believe that a 5-day quarantine or isolation period is sufficient for any COVID-19 infection.

On 5/06/22, the United States had 77,116 documented new infections. There were also 291 deaths. In the United States the number of hospitalized patients had been decreasing in many areas. Now there are 1,724  patients who are seriously or critically ill; that number was 1,512 two weeks ago. The number of critically ill patients has increased by 212 in the last 14 days, while at least 6,232 new deaths occurred (a decrease of 19 deaths per day from the previous 14 days). The number of critically ill patients has increased for the first time in nineteen 14-day periods. Patients are still dying each day (average 445/day). Omicron BA.2  variants causing infections should continue to increase and critically ill patients may continue to increase. Deaths usually lag two to four weeks behind exponential increase in infections so we will have to see how lethal BA.2.12.1 infections are in a month. Infections with a BA.1, and BA.2 will not prevent infections with BA.2.12.1. There have already been reports out of Israel of patients infected with BA.1 being later reinfected with BA.2. 

As of 5/06/22, we have had 1,024,386 deaths and 83,534,060 SARS-CoV-2 infections in the United States. We have had 905,971 new infections in the last 14 days. We were adding an average of 452,985 infections every seven days. For the pandemic in the United States we are averaging one death for every 81.5 infections reported for each death or over 12,263 deaths for each one million infections. As of 5/06/22, thirty-seven states have had greater than 500,000 total infections, and 36 states have had greater than 5,000 total deaths. Seventeen states (Virginia, Missouri, North Carolina, Indiana, Tennessee, Massachusetts, Ohio, Michigan, Georgia, Illinois, New Jersey, Pennsylvania, Florida, Texas, New York, Arizona and California) have had greater than 20,000 deaths. Four states (Florida, Texas, New York, and California) have had greater than 68,000 deaths. California and Texas have each had greater than 85,000 deaths with California having 90,804 deaths (20th most deaths in the world). 

On 11/20/20 in the United States, 3.70% of the population had a documented SARS-CoV-2 infection. California was ranked 41st in infection percentage at 2.77%. On 11/20/21 in North Dakota, 9.18% of the population was infected (ranked #1), and in South Dakota, 8.03% of the population was infected (ranked #2). As of 5/06/22, in the United States, 24.96% of the population has had a documented SARS-CoV-2 infection. In the last 17 months, 22.27% of our country became infected with SARS-CoV-2. On 11/20/20, there were 260,331 (cumulative) deaths in the US from SARS-CoV-2. In the last 17 months, there were 764,255 new deaths from SARS-CoV-2. For fourteen of those months, vaccines have been available to all adults. During these fourteen months, 453,289 people have died of SARS-CoV-2 infections. Most of the hospitalizations and deaths could have been prevented by vaccination, proper masking, and social distancing. 

As of 5/06/22, California was ranked 37th in infection percentage at 23.50%. In California 19.66% of Californians were infected in the last 17 months. As of 5/06/22 forty-five states have had greater than 20% of their population infected. Rhode Island was at 35,48% (ranked #1), Alaska was at 33.67% (ranked #2), North Dakota was at 31.72% (ranked #3), Kentucky was at 29.81% (ranked #4), Tennessee was at 29.78% (ranked #5), Utah was at 29.17% (ranked #6), South Carolina was at 28.69% (ranked #7), West Virginia was at 28.06% (ranked #8), Florida jumped to 27.97% (ranked #9). Wisconsin jumped to 27.87% (ranked #10), Arizona was at 27.82% (ranked #11), Arkansas was at 27.73% (ranked #12) and Texas was at 23.59% (ranked #36) of their population infected.

The table below shows that if we rank the US states with the highest death rates per million population within the world rankings, we see that Mississippi, Arizona and Alabama have the eighth highest death rates, New Jersey, Arkansas, West Virginia and Tennessee have the ninth highest COVID-19 deaths per million in the world. Louisiana had the tenth, New York was at eleventh,  Florida and Rhode Island were tied at twelth. The United States as a whole ranks 16th in the world for deaths per million population (3,095 deaths per million). California ranks 40th in the USA (and 36th in the world). If we look at the death rates per million in South Korea (452), Iceland (345), Japan (286), and Israel (1,152), they suggest that treatment outcomes are somehow different in these four countries. The same phenomenon can be seen in Scandinavia, where the death rate in Sweden is 1,839 per million, compared to 47 per million in Norway and 747 per million in Finland. The United States should have taken a closer look at how countries with low death rates (like South Korea, Iceland, Japan, Finland, and Norway) were preventing COVID-19 infections and treating COVID-19 patients. 

State or Country COVID-19 Deaths per million populationRank in USARanked within World
Mississippi4,1851st8th tied
New Jersey  3,7707th9th tied
Louisiana3,7168th10th 
New York 3,54413th11th 
Alabama3,9983rd8th tied
Arizona4,1482nd8th tied
Rhode Island  3,559  20th12th
Arkansas3,7806th9th tied
Florida3,44919th12th 
California2,29840th36th
USA3,09516th
Peru6,2961st
Bosnia-Herzegovina  4,8623rd
Hungary4,8124th
Montenegro4,3256th
Bulgaria5,3952nd
Czechia3,7429th
Brazil3,08416th
Georgia4,2297th
Sweden1,83957th
Israel1,15284th
Canada1,03691st
Finland747111th
Norway547125th
Japan286149th
Iceland345142nd
South Korea452129th

FDA-Approved Oral Drug Treatments for SARS-CoV-2

Pfizer has developed PAXLOVID™, an oral reversible inhibitor of C3-like protease of SARS-CoV-2. The drug inhibits this key enzyme that is crucial for virus production. The compound, also called Compound 6 (PF-07321332), is part of the drug combination PAXLOVID™ (PF-07321332; ritonavir), which just successfully completed a Phase 2-3 trial in humans in multiple countries. The preliminary results were announced on 11/5/21 by Pfizer. The results show that 89% of the hospitalizations and deaths were prevented in the drug treatment arm. The drug was administered twice a day for five days. No deaths occurred in the treatment group, and ten deaths occurred in the placebo group. The study was stopped by an independent data safety monitoring board, and the FDA concurred with this decision. Pfizer applied for an Emergency Use Authorization for this drug on 11/15/21. This drug was approved on 12/23/21. We have only been able to obtain PAXLOVID™ for two patients who we successfully treated with this drug obtained from CVS in Salinas (East Alisal Street; phone number 831-424-0026). They were expecting another shipment on 1/28/22. In my opinion, this agent, if more widely available, could markedly alter the course of every coronavirus infection throughout the world. 

Merck has developed the oral drug Molnupiravir, which induces RNA mutagenesis by viral RNA-dependent RNA polymerase of SARS-CoV-2 and other viruses. According to Kabinger et al, “Viral RNA-dependent RNA polymerase uses the active form of Molnupiravir, β-D-N4-hydroxycytidine triphosphate, as a substrate instead of cytidine triphosphate or uridine triphosphate. When the RNA-dependent RNA polymerase uses the resulting RNA as a template, β-D-N4-hydroxycytidine triphosphate directs incorporation of either guanine or adenine, leading to mutated (viral) RNA products. Analysis of RNA-dependent RNA polymerase–RNA complexes that contain mutagenesis products has demonstrated that β-D-N4-hydroxycytidine (the active form of Molnupiravir) can form stable base pairs with either guanine or adenine in RNA-dependent RNA polymerase explaining how the polymerase escapes proofreading and synthesizes mutated RNA” (quotation modified for clarity). The results of the phase 3 trial of Molnupiravir were published in the NEJM article “Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients” by Angélica Jayk Bernal, M.D. et al. (December 16, 2021 DOI: 10.1056/NEJMoa2116044). In this phase 3 study in the Molnupiravir group, 28 patients were hospitalized and one death occurred. In the placebo group, 53 patients were hospitalized and 9 died. Overall, 47% of hospitalizations and deaths were prevented by Molnupiravir. If you do a post hoc analysis and just look at deaths, Molnupiravir would prevent 89% of deaths. An Emergency Use Authorization by the FDA for Molnupiravir was approved on 12/24/21.The dose of Molnupiravir approved is four 200 mg capsules orally twice a day for five days. Diarrhea is reportedly a side effect in two percent of patients. I treated my first patient with Molnupiravir on 1/28/22. Currently more Molnupiravir is available weekly in the United States than PAXLOVID™ (see chart below; data from PHE.gov). Locally Molnupiravir is still available at CVS in Monterey (Fremont Blvd.; phone number: 831-375-5135) and CVS in Salinas (East Alisal Street; phone number 831-424-0026). 

FDA Approved Intramuscular Prophylaxis of SARS-CoV-2 Immunocompromised Patients

Evusheld (from AstraZeneca) contains two human monoclonal antibodies, Tixagevimab (150 mg in 1.5 mL) and Cilgavimab (150 mg in 1.5 mL), in separate vials. According to the manufacturer, “Tixagevimab and Cilgavimab are two recombinant human IgG1κ monoclonal antibodies with amino acid substitutions to extend antibody half-life (YTE), reduce antibody effector function, and minimize the potential risk of antibody-dependent enhancement of disease (TM). Tixagevimab and Cilgavimab can simultaneously bind to non-overlapping regions of the receptor binding domain (RBD) of SARS-CoV-2 spike protein. Tixagevimab, Cilgavimab, and their combination bind to spike protein with equilibrium dissociation constants of KD = 2.76 pM, 13.0 pM and 13.7 pM, respectively, blocking its interaction with human ACE2, the SARS-CoV-2 receptor, which is required for virus attachment. Tixagevimab, Cilgavimab, and their combination blocked RBD binding to human ACE2 with IC50 values of 0.32 nM (48 ng/mL), 0.53 nM (80 ng/mL), and 0.43 nM (65 ng/mL), respectively.” Each monoclonal antibody is administered intramuscularly to immunocompromised patients in two separate injections every six months. Evusheld availability in California is limited and has been rationed/distributed by our local Public Health Department only to hospitals. Physicians in Monterey County who want to receive a distribution (or redistribution) of Evusheld need to be added to the list of eligible facilities by the State Therapeutics group. The first step is for the Monterey County EMS Agency (phone: 831-755-5713) to make a request to the State Therapeutics group to have the facility added to the system for further verification.  Due to extremely limited availability, evidently the State Therapeutics group is currently only considering additions on a case by case basis.  Physicians who wish to submit their facility for consideration will need to provide the following information to the Monterey County EMS Agency:

  1. Facility/Provider Name for Registration
  2. Provider Type (Hospital, Pharmacy, Etc)
  3. Shipping Address
  4. Contact Name(s)
  5. Contact Email(s)
  6. Contact Phone Number(s)

As for my immunocompromised patients: We provided this information by email to the Monterey County EMS Agency on 1/26/22 and will update you when or if we become an eligible provider and receive our first doses of Evusheld. On 2/24/22, the FDA revised its dosing guidance for Evusheld, doubling the dosage of its two components, Tixagevimab and Cilgavimab, from 150 mg each to 300 mg each. They explain, “Based on the most recent information and data available, Evusheld may be less active against certain Omicron subvariants. The dosing regimen was revised because available data indicate that a higher dose of Evusheld may be more likely to prevent infection by the COVID-19 Omicron subvariants BA.1 and BA.1.1 than the originally authorized Evusheld dose.” Patients who have already received their first administration of Evusheld intramuscularly will need to contact their healthcare provider to get a second 150 mg injection of Tixagevimab and Cilgavimab. If you have not received Evusheld yet, the correct dose is 3 mL/300 mg of each monoclonal antibody injected intramuscularly. This large volume necessitates administration of the antibodies in the gluteus, with two separate injections.

A New Possible Indication for an Older FDA-Approved Antiviral Drug 

Remdesivir was the first FDA-approved Emergency Use Authorization drug for the treatment of SARS-CoV-2 infected patients. In their January 2021 paper in Nature Communications, Kokic et al explained the mechanism of Remdesivir’s action on SARS-CoV-2: “The active form of remdesivir acts as a nucleoside analog and inhibits the RNA-dependent RNA polymerase (RdRp) of coronaviruses including SARS-CoV-2. Remdesivir is incorporated by the RdRp into the growing RNA product and allows for addition of three more nucleotides before RNA synthesis stalls. Addition of the fourth nucleotide following Remdesivir incorporation into the RNA product is impaired by a barrier to further RNA translocation. This translocation barrier causes retention of the RNA 3ʹ-nucleotide in the substrate-binding site of the RdRp and interferes with entry of the next nucleoside triphosphate, thereby stalling RNA-dependent RNA polymerase. In the structure of the Remdesivir-stalled state, the 3ʹ-nucleotide of the RNA product is matched and located with the template base in the active center, and this may impair proofreading by the viral 3ʹ-exonuclease.” 

A recent study by Gottlieb et al of intravenous Remdesivir to prevent disease progression, whose design was similar to the study designs used for PAXLOVID™ and Molnupiravir, was published in the New England Journal of Medicine on 1/27/22. The study resulted in an 87% lower risk of hospitalization or death than in the placebo group with a similar adverse events occurrence (42.3% and 46.3% respectively). The FDA may allow approval of outpatient intravenous Remdesivir over three days (200 mg IV on day one followed by 100 mg IV daily on days two and three) in high risk non-hospitalized SARS-CoV-2 infected patients.

With the exception of Evusheld, all of the therapies listed above, with the exception of sotrovimab, can be used in Omicron-infected patients. Other previously approved monoclonal antibodies will not work for Omicron.

The Threat of SARS-CoV-2 Variants

In response to the need for “easy-to-pronounce and non-stigmatising labels,” at the end of May, the World Health Organization assigned a letter from the Greek alphabet to each SARS-CoV-2 variant. GISAID, Nextstrain, and Pango will continue to use the previously established nomenclature. For our purposes, we’ll be referring to each variant by both its Greek alphabet letter and the Pango nomenclature. 

The WHO has sorted variants into two categories: Variants of Concern (VOC) and Variants of Interest (VOI). The criteria for Variants of Concern are as follows:

  • Increase in transmissibility or detrimental change in COVID-19 epidemiology; or 
  • Increase in virulence or change in clinical disease presentation; or 
  • Decrease in effectiveness of public health and social measures or available diagnostics, vaccines, therapeutics.  

The WHO categorizes the following five variants as Variants of Concern (VOC):

Source: World Health Organization

The criteria for Variants of Interest (VOI) are as follows:

  • has been identified to cause community transmission/multiple COVID-19 cases/clusters, or has been detected in multiple countries; OR  
  • is otherwise assessed to be a VOI by WHO in consultation with the WHO SARS-CoV-2 Virus Evolution Working Group. 

The WHO categorizes the following six variants as Variants of Interest (VOI):

According to the UK Health Security Agency Technical Briefing from 2/25/22, “A putative Delta and Omicron recombinant has been identified in the UK, with likely parental lineages AY.4.2.2 and BA.1.1 and a breakpoint in non-structural protein 3 (nsp3). The presence of 34 genomes sampled between 7 January 2022 and 14 February 2022 suggest that this recombinant is able to transmit.” GISAID has also begun publishing data about a recombinant of Delta AY.4 and Omicron BA.1, first identified in France. According to GISAID data, this variant has also been detected in Denmark, Germany, the Netherlands, and the United States. Forbes 

We will need to monitor for this Delta-Omicron recombinant variant in the United States as well. 

Omicron cases sequenced as of 5/8/22:

GISAID

GISAID

Map of Omicron sequenced transmissions:

GISAID

Delta cases sequenced as of 5/8/22: 

GISAID

Map of Delta sequenced transmissions:

GISAID

GKA (AY.4/BA.1) cases sequenced as of 5/8/22:

GISAID

B.1.640 cases sequenced as of 5/8/22:

GISAID

Watching World Data

Over the next few months, we’ll be paying close attention to correlations between the SARS-CoV-2 data, the number of isolates identified in various countries and states, and the non-pharmaceutical interventions (like mask mandates and lockdowns) put in place by state and national governments. Data on infections, deaths, and percent of population infected was compiled from Worldometers. Data for this table for SARS-CoV-2 Isolates Currently Known in Location was compiled from GISAID and the CDC. It’s worth noting that GISAID provided more data than the CDC.

LocationTotal Infections as of 5/06/22New Infections on 5/06/22Total DeathsNew Deaths on 5/06/22% of Pop.InfectedSARS-CoV-2 Isolates Currently Known in LocationNational/ State Mask MandateCurrently in Lockdown
World516,495,714(7,985,986 new infections in 14 days).514,7036,274,548(34,384 new deaths in last 14 days)2,0066.62%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)A lineage isolateV01.V2 (Tanzania)APTK India VOC 32421Delta/B.1.617.2 (India)BV-1 (Texas, USA)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Theta/P.3 (Philippines) Mu/B.1.621 (Colombia)C.1.2 (South Africa 2% of isolates in July 2021)R1 (Japan)Omicron/B.1.1.529 + BA.1 + BA.2 + BA.3 (South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)Four new recombinants 12/31 to 3/22)NoNo
USA83,534,060(ranked #1) 905,971 new infections in the last 14 days.77,116(ranked #2)1,024,386(ranked #1)6,232 new deaths in the last 14 days. 29124.96%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)BV-1 (Texas, USA)Theta/P.3 (Philippines) Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)R1(Japan)         Omicron/B.1.1.529 + BA.1 + BA.2 (South Africa November 2021)B.1.640.1 (Congo/France)Recombinant Delta AY.119.2- Omicron BA.1.1 (Tennessee, USA 12/31/21)NoNo
Brazil30,543,908(ranked #3) 497,143 new infections in the last 14 days. 19,725 (ranked #9)664,143(ranked #2)17814.18%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Zeta/P.2 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
India43,018,032(ranked #2); 44,151 new infections in 2 weeks.4,195524,024(ranked #3)223.06%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)APTK India VOI 32421Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Iota/B.1.526 (USA-NYC) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
United Kingdom22,114,034(ranked #6; was #6 thirty-two weeks ago; 180,828 new infections in 2 weeks.6,551(ranked 15th in the world).176,212(ranked #7 in world)22832.26%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)C.1.2 (South Africa)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)XD (AY.4/BA.1) recombinantXF (Delta/BA.1) recombinantXE (BA.1/BA.2) recombinantNoNo
California, USA9,288,773(ranked #13 in the world;  44,240 new infections in the last 14 days).39,51490.804 (ranked #20 in world)5523.50%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Zeta/P.2 (Brazil)Delta/B.1.617.2 (India)Theta/P.3 (Philippines) Kappa/B.1.617.1 (India)Lambda/C.37 (Peru) Mu/B.1.621 (Colombia) Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Mexico5,740,080(ranked #20) 8,445 new infections in 14 days).———324,350(ranked #5)——–4.36%B2 lineageAlpha/B.1.1.7 (UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
South Africa3,827,378(ranked #30; 71,869 new infections in 14 days).9,253100,505 (ranked #18)346.30%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)       C.1.2 (South Africa, July 2021)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
Canada3,787,378(ranked #27, was 26th sixteen weeks ago; 95,613 new infections in 14 days).8,55737,977(ranked #26)429.29% .B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Kappa/B.1.617.1 (India)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
Poland5,999,513(ranked #19; 43,262 new infections in 14 days). 607116,124 (ranked #15)2615.88%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 + (South Africa November 2021),Omicron/B.1.1.529 +BA.3 NoNo
Turkey15,040,238(ranked #10, 26,622 new infections in 14 days).1,74398,826 (ranked #19)717.48% B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gamma/P.1 (Brazil)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
Russia18,216,719(ranked #7), 96,857 new infections in 14 days).5,541376,696(ranked #4 in world)13612.47%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Delta/B.1.617.2 (India)R1 (Japan) B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Argentina9,083,673(ranked #13; 22,650 new infections in 14 days).———–128,194 (ranked #14 in world)——–19.76%B2 lineageAlpha/B.1.1.7 (UK)Eta/B.1.525 (Nigeria/UK)Beta/B.1.351 (SA)Epsilon/B.1.427 + B.1.429 (USA)*Gama/P.1 (Brazil)Delta/B.1.617.2 (India)Lambda/C.37 (Peru)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Colombia6,093,645(ranked #18, 2,842 new infections in 14 days).———–139,809 (ranked #12 in the world)———11.74%B2 lineageAlpha/B.1.1.7 (UK)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Delta/B.1.617.2 (India)Epsilon/B.1.427 + B.1.429 (USA)*Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Peru3,569,026(ranked #35, 9,683 new infections in 14 days). 334212,913(ranked #6)710.55%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Gamma/P.1 (Brazil)Iota/B.1.526 (USA-NYC)Lambda/C.37 (Peru)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)NoNo
Indonesia6,097,986(ranked #18; 54,720 new infections in 14 days)245156,357 (ranked #9)172.16%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Eta/B.1.525 (Nigeria/UK)Theta/P.3 (Philippines) Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)B.1.640.1 (Congo/France)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)
NoNo
Iran7,224,431 9,527 new infections in last 14 days(ranked 16th; was 12th  thirty-two weeks ago)375141,157 (ranked #11)128.40%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)


NoNo
Spain12,009,059(ranked 11th;   381,572  new infections in 14 days).18,526104,869 (ranked #17)6725.66%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India)Beta/B.1.351 (SA)Gamma/P.1 (Brazil)Epsilon/B.1.427 + B.1.429 (USA)*Eta/B.1.525 (Nigeria/UK)Iota/B.1.526 (USA-NYC)Kappa/B.1.617.1 (India)Mu/B.1.621 (Colombia)Omicron/B.1.1.529 + BA.1 (South Africa November 2021)B.1.640.1 (Congo/France)NoNo
France28,890,139 (ranked #4; 725,733 new infections in the last 14 days).40,224 (ranked #4)146,608 (ranked #10)11044.08%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)B.1.640.1 (Congo/France)B.1.640.2 (Cameroon/France)GKA (AY.4/BA.1) recombinantNoNo
Germany25,289,590(ranked #5; 1,279,822 new infections in 14 days.).86,026 (ranked #1)136,812 (ranked #13)33630.00%
B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
Hungary1,903,200 (ranked #43; 12,237new infections in 14 days).
———46,266 (ranked #23)——–19.79%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Romania2,898,258(ranked #38; 11,000 new infections in 14 days).73065,554 (ranked#20)915.25%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
South Korea17,464,782 (ranked 8th) ; 709,727 new infections in 14 days).26,714(ranked#7)23,206 (ranked #39); 4834.01%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Ukraine5,002,870(ranked #22; 20,621 new infections in 14 days),——–108,411 (ranked #16)——–11.56%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Vietnam10,670,570(ranked #12; 126,246 new infections in 14 days).3,81943,051 (ranked #24)610.78%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)NoNo
Netherlands8,057,700 (ranked #14; 22,097 new infections in 14 days).1,30322,270 (ranked #41)146.83%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo
Denmark2,970,809, (ranked #37) 12,283  new infections in 14 days8076,266 (ranked #81)850.95%B2 lineageAlpha/B.1.1.7 (UK)Delta/B.1.617.2 (India) Delta/B.1.617.2 (India) Omicron/B.1.1.529 South Africa November 2021)GKA (AY.4/BA.1) recombinantNoNo




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